1 00:00:05,120 --> 00:00:09,200 I'M CAROL THIELE, DEPUTY CHIEF 2 00:00:09,200 --> 00:00:11,800 OF PEDIATRIC ONCOLOGY BRANCH, 3 00:00:11,800 --> 00:00:12,640 SENIOR INVESTIGATOR IN THE 4 00:00:12,640 --> 00:00:14,840 BRANCH, I HAVE THE HONOR OF 5 00:00:14,840 --> 00:00:16,640 BEING THE LONGEST SERVING 6 00:00:16,640 --> 00:00:18,160 MEMBER, I THINK, OF THE BRANCH, 7 00:00:18,160 --> 00:00:21,000 PERHAPS THE OLDEST AS WELL. 8 00:00:21,000 --> 00:00:26,920 I THINK TODAY WE'RE GOING TO 9 00:00:26,920 --> 00:00:28,640 CELEBRATE ACHIEVEMENTS IN CAR T 10 00:00:28,640 --> 00:00:30,400 CELL THERAPY, BUILDING ON A LONG 11 00:00:30,400 --> 00:00:33,240 HISTORY OF ACHIEVEMENT IN THE 12 00:00:33,240 --> 00:00:35,440 PEDIATRIC ONCOLOGY BRANCH. 13 00:00:35,440 --> 00:00:39,480 AND FIRST STARTED BY ART LEVINE 14 00:00:39,480 --> 00:00:42,760 IN THE 70s, WHERE WE DEVELOPED 15 00:00:42,760 --> 00:00:52,480 SOME OF THE FIRST THERAPY FOR 16 00:00:52,480 --> 00:00:55,240 TREATING TEDDY, THE BOY IN THE 17 00:00:55,240 --> 00:00:56,680 BUBBLE WITH IMMUNODEFICIENCIES. 18 00:00:56,680 --> 00:00:58,960 LATER THE FELLOW IN CHARGE OF 19 00:00:58,960 --> 00:01:06,360 TREATING TEDDY BECAME OUR BRANCH 20 00:01:06,360 --> 00:01:09,080 CHIEF, PHIL PEAZO'S, DURING HIS 21 00:01:09,080 --> 00:01:12,240 YEARS HERE A RICH ENVIRONMENT 22 00:01:12,240 --> 00:01:14,000 FOR US, SOME FIRST TREATMENTS 23 00:01:14,000 --> 00:01:15,840 FOR KIDS WITH HIV, DEVELOPMENT 24 00:01:15,840 --> 00:01:17,480 OF PSYCHOSOCIAL SUPPORTS FOR 25 00:01:17,480 --> 00:01:23,000 THESE TREATMENTS, AND THEIR 26 00:01:23,000 --> 00:01:23,800 FAMILIES. 27 00:01:23,800 --> 00:01:26,040 DAVID POPLAK AND GROUND-BREAKING 28 00:01:26,040 --> 00:01:28,720 STUDIES ON PREVENTION OF CNS 29 00:01:28,720 --> 00:01:36,360 TOXICITY FOR LEUKEMIA, IN THE 30 00:01:36,360 --> 00:01:42,960 REGIMENS FOR LYMPHOMA. 31 00:01:42,960 --> 00:01:47,000 LEE HELLMUND BECAME THE CHIEF, 32 00:01:47,000 --> 00:01:50,840 BROUGHT TO THE FORE MOLECULAR 33 00:01:50,840 --> 00:01:52,440 ONCOLOGY AND RECRUITMENT OF SOME 34 00:01:52,440 --> 00:01:55,840 OF THE YOUNGER NEWER MEMBERS OF 35 00:01:55,840 --> 00:01:58,600 THE BRANCH, AND DEVELOPING 36 00:01:58,600 --> 00:01:59,760 IMMUNOTHERAPY WITH RECRUITMENT 37 00:01:59,760 --> 00:02:02,080 OF CRYSTAL MAKEL AND IN FACT 38 00:02:02,080 --> 00:02:03,280 CRYSTAL LATER BECAME THE BRANCH 39 00:02:03,280 --> 00:02:05,800 CHIEF AND IT WAS REALLY AT THIS 40 00:02:05,800 --> 00:02:07,440 TIME WHEN IMMUNOTHERAPY CAME TO 41 00:02:07,440 --> 00:02:08,800 THE FORE. 42 00:02:08,800 --> 00:02:11,480 YOU'LL HEAR ABOUT THESE. 43 00:02:11,480 --> 00:02:13,360 ALSO BUILDING ON THIS SUCCESS WE 44 00:02:13,360 --> 00:02:16,320 ALSO HAVE -- I'M HERE TO 45 00:02:16,320 --> 00:02:22,440 INTRODUCE OUR CURRENT BRANCH 46 00:02:22,440 --> 00:02:29,840 CHIEF, DR. WEEDMAN, FOR TREATING 47 00:02:29,840 --> 00:02:35,400 METHYLTREXATE OVERDOSES. 48 00:02:35,400 --> 00:02:43,360 I'D LIKE TO DR. BRIGITTE 49 00:02:43,360 --> 00:02:43,920 WEEDMAN. 50 00:02:43,920 --> 00:02:46,120 >> THANK YOU FOR THIS AMAZING 51 00:02:46,120 --> 00:02:46,440 SYMPOSIUM. 52 00:02:46,440 --> 00:02:49,360 WE HAVE THE NEW FELLOWS HERE AS 53 00:02:49,360 --> 00:02:54,640 WELL TODAY, AND I THINK CAROL'S 54 00:02:54,640 --> 00:02:56,960 BACKGROUND SHOWS A LOT OF 55 00:02:56,960 --> 00:02:59,800 HISTORY AND COLLABORATION. 56 00:02:59,800 --> 00:03:01,360 WE'RE CELEBRATING THE SUCCESSES 57 00:03:01,360 --> 00:03:04,400 IN CAR T CELL THERAPY, NOW TEN 58 00:03:04,400 --> 00:03:07,200 YEARS, AND IT STARTED WITH A 59 00:03:07,200 --> 00:03:12,600 TEAM IN THE POB, FOR CAR T CELL 60 00:03:12,600 --> 00:03:19,120 THERAPY AND POB, AND YOU SEE THE 61 00:03:19,120 --> 00:03:24,960 LEADERS AT THE TIME. 62 00:03:24,960 --> 00:03:28,800 THIS WAS A VERY EXCITING TIME 63 00:03:28,800 --> 00:03:31,280 BUT THEN PEOPLE LEFT TO DO GREAT 64 00:03:31,280 --> 00:03:33,840 WORK IN OTHER PLACES. 65 00:03:33,840 --> 00:03:37,560 AND BY 2018, THIS WAS THE POB 66 00:03:37,560 --> 00:03:38,320 LEUKEMIA TEAM. 67 00:03:38,320 --> 00:03:40,320 NIRALI USED TO SHOW THIS 68 00:03:40,320 --> 00:03:40,720 PICTURE. 69 00:03:40,720 --> 00:03:44,120 AND OF COURSE, THIS DID NOT 70 00:03:44,120 --> 00:03:47,200 DETER NIRALI TO BUILD A FIRST 71 00:03:47,200 --> 00:03:48,560 CLASS TOP NOTCH CLINICAL TEAM. 72 00:03:48,560 --> 00:03:50,600 THIS IS SOME OF THE CLINICAL 73 00:03:50,600 --> 00:03:50,920 MEMBERS. 74 00:03:50,920 --> 00:03:53,320 I'M ONLY FOCUSING ON POB TODAY. 75 00:03:53,320 --> 00:03:55,280 WE HAVE GUESTS HERE, SO MANY 76 00:03:55,280 --> 00:04:01,120 COLLABORATORS, BUT THIS IS THE 77 00:04:01,120 --> 00:04:06,160 CORE CLINICAL TEAM, BONNIE, 78 00:04:06,160 --> 00:04:08,240 HAMIN, AND DR. PERBERMA, AN 79 00:04:08,240 --> 00:04:10,680 EXCELLENT TEAM OF NURSES, 80 00:04:10,680 --> 00:04:13,040 PCCs, FELLOWS, RESEARCH 81 00:04:13,040 --> 00:04:13,920 MANAGERS. 82 00:04:13,920 --> 00:04:15,680 VERY IMPORTANTLY, REALLY 83 00:04:15,680 --> 00:04:17,640 STRATEGIC, WE HAVE A NEW BASIC 84 00:04:17,640 --> 00:04:20,920 EFFORT IN THE BRANCH IN CAR T 85 00:04:20,920 --> 00:04:22,920 CELL THERAPY, IN LEUKEMIAS, THIS 86 00:04:22,920 --> 00:04:25,840 IS LED BY DR. NAOMI TAYLOR. 87 00:04:25,840 --> 00:04:29,240 I'M ALSO HIGHLIGHTING CHRIS 88 00:04:29,240 --> 00:04:30,360 CHEN, NIRALI'S BIOLOGIST, TAKING 89 00:04:30,360 --> 00:04:32,960 THE EFFORTS, BUT MANY MORE IN 90 00:04:32,960 --> 00:04:33,400 POB. 91 00:04:33,400 --> 00:04:39,240 AS I MENTIONED, OUTSIDE OF THE 92 00:04:39,240 --> 00:04:40,640 PEDIATRIC ONCOLOGY BRANCH. 93 00:04:40,640 --> 00:04:43,400 TWO FELLOWS MADE IT THROUGH OUR 94 00:04:43,400 --> 00:04:44,600 ONE-YEAR FELLOWSHIP IN PEDIATRIC 95 00:04:44,600 --> 00:04:45,040 IMMUNOTHERAPY. 96 00:04:45,040 --> 00:04:46,080 I'LL SHOW YOU WHERE THEY HAVE 97 00:04:46,080 --> 00:04:48,880 GONE IN A MOMENT. 98 00:04:48,880 --> 00:04:51,800 AND THEN WONDERFUL ASPECT OF THE 99 00:04:51,800 --> 00:04:53,120 LEUKEMIA TEAM AND IMMUNOTHERAPY 100 00:04:53,120 --> 00:04:55,520 EXPERTISE, WE'VE BEEN ABLE TO 101 00:04:55,520 --> 00:04:57,600 BUILD A SOLID TUMOR 102 00:04:57,600 --> 00:04:58,480 IMMUNOTHERAPY TEAM, I'M SHOWING 103 00:04:58,480 --> 00:05:07,320 SOME OF THE INVESTIGATORS HERE, 104 00:05:07,320 --> 00:05:09,040 ROSY KAPLAN AND OTHERS, AND OF 105 00:05:09,040 --> 00:05:09,760 COURSE CAROL. 106 00:05:09,760 --> 00:05:12,640 THIS IS A GREAT TEAM THAT IS NOW 107 00:05:12,640 --> 00:05:15,760 BUILDING CAR T CELL THERAPIES 108 00:05:15,760 --> 00:05:22,480 FOR OSTEOSARCOMA, 109 00:05:22,480 --> 00:05:22,800 NEUROBLASTOMA. 110 00:05:22,800 --> 00:05:26,600 IT'S BEEN HELPFUL TO HAVE PEOPLE 111 00:05:26,600 --> 00:05:27,840 LIKE THIS HELPING THE SOLID 112 00:05:27,840 --> 00:05:29,800 TUMOR TEAM IN DEVELOPING THE 113 00:05:29,800 --> 00:05:33,320 PROTOCOLS BUT ALSO PROVIDING THE 114 00:05:33,320 --> 00:05:34,080 EXPERTISE AS WE'RE SEEING CAR T 115 00:05:34,080 --> 00:05:36,040 CELL TOXICITY IN THE SOLID TUMOR 116 00:05:36,040 --> 00:05:36,520 PATIENTS. 117 00:05:36,520 --> 00:05:38,560 SO IT IS A REAL TEAM EFFORT. 118 00:05:38,560 --> 00:05:42,600 MY LAST SLIDE IS TO SHOW YOU OUR 119 00:05:42,600 --> 00:05:42,960 PHILOSOPHY. 120 00:05:42,960 --> 00:05:45,320 ANYBODY WHO LEAVES THE POB STAYS 121 00:05:45,320 --> 00:05:49,640 TO BE A POB MEMBER. 122 00:05:49,640 --> 00:05:51,120 IT'S THE POB DIASPORA. 123 00:05:51,120 --> 00:05:54,520 WE HAVE POB COLORADO, WE HAVE 124 00:05:54,520 --> 00:06:00,000 POB CALIFORNIA, POB TEXAS, 125 00:06:00,000 --> 00:06:01,720 MIDWEST, TEXAS, PHILADELPHIA, 126 00:06:01,720 --> 00:06:02,840 FLORIDA, AND INTERNATIONAL POB 127 00:06:02,840 --> 00:06:07,760 WITH FELLOWS AND LEADERS NOW IN 128 00:06:07,760 --> 00:06:08,960 IMMUNOTHERAPY IN ISRAEL, 129 00:06:08,960 --> 00:06:10,560 ENGLAND, GERMANY, IT'S A 130 00:06:10,560 --> 00:06:11,480 SNAPSHOT, NOT COMPLETE. 131 00:06:11,480 --> 00:06:14,080 I WOULD LIKE TO HAND OVER TO 132 00:06:14,080 --> 00:06:16,280 NIRALI SHAH AND REALLY LOOK 133 00:06:16,280 --> 00:06:18,600 FORWARD TO THIS SYMPOSIUM TODAY, 134 00:06:18,600 --> 00:06:19,440 TO CELEBRATING THE SUCCESSES 135 00:06:19,440 --> 00:06:25,440 OVER THE PAST TEN YEARS. 136 00:06:25,440 --> 00:06:30,400 [APPLAUSE] 137 00:06:30,400 --> 00:06:32,640 >> WE'RE GOING TO HAVE TWO 138 00:06:32,640 --> 00:06:35,240 VIDEOS FROM FORMER POB. 139 00:06:35,240 --> 00:06:38,160 FIRST IS ALAN WAYNE. 140 00:06:38,160 --> 00:06:40,000 >>GREETINGS FROM LOS ANGELES. 141 00:06:40,000 --> 00:06:45,560 I HOPE EVERYONE AT THE POB AND 142 00:06:45,560 --> 00:06:49,160 ACROSS THE INTRAMURAL NIH IS 143 00:06:49,160 --> 00:06:50,720 DOING WELL. 144 00:06:50,720 --> 00:06:57,840 PROGRAM BEGIN IN SUMMER OF 2009, 145 00:06:57,840 --> 00:07:02,120 STEVE ROSENBERG AND JIM 146 00:07:02,120 --> 00:07:02,400 COKENBERGER. 147 00:07:02,400 --> 00:07:05,040 THEY WONDERED IF IT WAS TIME TO 148 00:07:05,040 --> 00:07:06,040 EXPAND INTO PEDIATRICS. 149 00:07:06,040 --> 00:07:08,560 WHAT BEGAN AS A PLANNED 150 00:07:08,560 --> 00:07:11,720 AMENDMENT TO END A PEDIATRIC ARM 151 00:07:11,720 --> 00:07:13,040 TO THEIR TRIAL, EVENTUALLY 152 00:07:13,040 --> 00:07:16,960 EVOLVED INTO THE POB'S FIRST CAR 153 00:07:16,960 --> 00:07:17,440 T CELL PROTOCOL. 154 00:07:17,440 --> 00:07:19,840 I DON'T KNOW IF STEVE OR JIM ARE 155 00:07:19,840 --> 00:07:21,560 PRESENT TODAY, BUT TO BE FRANK, 156 00:07:21,560 --> 00:07:24,320 I THINK THEY GREW WEARY OF THE 157 00:07:24,320 --> 00:07:25,240 MULTITUDE OF CHILD-SPECIFIC 158 00:07:25,240 --> 00:07:28,520 ISSUES REQUIRED FOR THE PROTOCOL 159 00:07:28,520 --> 00:07:28,960 AMENDMENT. 160 00:07:28,960 --> 00:07:37,160 THE PEDIATRIC WORLD OF CCs AND 161 00:07:37,160 --> 00:07:38,080 MILLIGRAMS PER KILOGRAM DOSING 162 00:07:38,080 --> 00:07:40,120 FILLED PAGES IN THE PROTOCOL 163 00:07:40,120 --> 00:07:45,680 DOCUMENT. 164 00:07:45,680 --> 00:07:50,520 WE DECIDED TO CREATE 12C 0112. 165 00:07:50,520 --> 00:07:53,360 IN PARALLEL, THIS ALLOWED US TO 166 00:07:53,360 --> 00:07:54,240 MODIFY THE MANUFACTURING. 167 00:07:54,240 --> 00:07:56,200 SOME OF YOU MAY RECALL I HAD 168 00:07:56,200 --> 00:07:57,520 TRAINED AND WORKED IN 169 00:07:57,520 --> 00:07:58,840 TRANSFUSION MEDICINE AND BLOOD 170 00:07:58,840 --> 00:07:59,080 BANKING. 171 00:07:59,080 --> 00:08:02,080 I WAS KEEN TO MOVE AWAY FROM THE 172 00:08:02,080 --> 00:08:05,720 ORIGINAL RESEARCH LAB BASED OPEN 173 00:08:05,720 --> 00:08:09,880 WELL MANUFACTURING PROCESS. 174 00:08:09,880 --> 00:08:13,800 WORKING WITH MARIANA CABITANO, 175 00:08:13,800 --> 00:08:16,760 DAVE AND CRYSTAL AND TREY, WE 176 00:08:16,760 --> 00:08:19,200 SPEND $150,000 OF OUR POB BUDGET 177 00:08:19,200 --> 00:08:21,200 IN 18 MONTHS TO GET THE NEW 178 00:08:21,200 --> 00:08:23,360 PROCESS READY FOR HUMAN TRIALS. 179 00:08:23,360 --> 00:08:25,960 THAT CULMINATED IN THE METHODS 180 00:08:25,960 --> 00:08:29,240 PAPER WITH BARBARA AS FIRST 181 00:08:29,240 --> 00:08:30,240 AUTHOR, IN 2013. 182 00:08:30,240 --> 00:08:32,960 THOSE WERE THE METHODS USED FOR 183 00:08:32,960 --> 00:08:35,360 THE FIRST TRIAL MODIFIED FURTHER 184 00:08:35,360 --> 00:08:37,960 FOR SUBSEQUENT TESTING IN THEIR 185 00:08:37,960 --> 00:08:42,680 TRIALS WHICH LED TO FDA 186 00:08:42,680 --> 00:08:44,680 APPROVALS, FIRST IN OCTOBER OF 187 00:08:44,680 --> 00:08:45,520 2017. 188 00:08:45,520 --> 00:08:46,960 NOW FOR A FEW OTHER HISTORICAL 189 00:08:46,960 --> 00:08:52,640 POINTS THAT MAY BE OF INTEREST. 190 00:08:52,640 --> 00:08:56,480 AS HOLIDAYS APPROACHED IN 2011, 191 00:08:56,480 --> 00:08:58,400 CRYSTAL PRESSURED US TO COMPLETE 192 00:08:58,400 --> 00:09:03,400 APPLICATIONS TO MEET END OF YEAR 193 00:09:03,400 --> 00:09:03,960 SUBMISSION DEADLINES. 194 00:09:03,960 --> 00:09:06,480 PREPARING TO LEAVE THE COUNTRY 195 00:09:06,480 --> 00:09:07,800 ON VACATION, AND I HAD BEEN 196 00:09:07,800 --> 00:09:10,440 PLANNING TO COMPLETE OVER THE 197 00:09:10,440 --> 00:09:11,440 HOLIDAYS, I REMEMBER THINKING, 198 00:09:11,440 --> 00:09:13,080 WHAT'S THE DIFFERENCE IN WAITING 199 00:09:13,080 --> 00:09:14,320 ONE MORE MONTH, WE HAD BEEN 200 00:09:14,320 --> 00:09:16,600 WORKING FOR 2 1/2 YEARS. 201 00:09:16,600 --> 00:09:18,760 I WILL ADMIRE CRYSTAL FOR THAT 202 00:09:18,760 --> 00:09:20,600 PRESSURE AND THAT APPROACH 203 00:09:20,600 --> 00:09:21,800 BECAUSE WE'RE NEVER FAST ENOUGH 204 00:09:21,800 --> 00:09:24,000 OR FAR ENOUGH ALONG FOR ALL OF 205 00:09:24,000 --> 00:09:25,920 OUR PATIENTS. 206 00:09:25,920 --> 00:09:29,080 SO WE INDEED MET THOSE 207 00:09:29,080 --> 00:09:29,360 DEADLINES. 208 00:09:29,360 --> 00:09:31,680 ONE FUNNY NOTE RELATED TO 209 00:09:31,680 --> 00:09:32,680 CRYSTAL'S URGENCY, SHE PUSHED 210 00:09:32,680 --> 00:09:35,640 HARD AT EVERY STEP OF THE WAY, 211 00:09:35,640 --> 00:09:37,400 INCLUDING TO PUBLISH OUR INITIAL 212 00:09:37,400 --> 00:09:41,320 RESULTS OF THAT FIRST CD19 CAR, 213 00:09:41,320 --> 00:09:42,640 PHASE 1 TRIAL. 214 00:09:42,640 --> 00:09:46,720 THAT PAPER APPEARED ONLINE IN 215 00:09:46,720 --> 00:09:51,080 "LANCET," ON MONDAY, OCTOBER 13, 216 00:09:51,080 --> 00:09:51,520 2014. 217 00:09:51,520 --> 00:09:53,800 THREE DAYS LATER, ON THURSDAY, 218 00:09:53,800 --> 00:09:56,800 OCTOBER 16, THE CHOP U PENN 219 00:09:56,800 --> 00:10:00,800 GROUP PUBLISHED THEIR CD19 CAR 220 00:10:00,800 --> 00:10:01,600 PHASE 1 RESULTS IN THE NEW 221 00:10:01,600 --> 00:10:02,640 ENGLAND JOURNAL OF MEDICINE. 222 00:10:02,640 --> 00:10:04,120 WE WERE CLASSMATES AND I WILL 223 00:10:04,120 --> 00:10:05,760 NEVER LET HIM FORGET WE BEAT HIM 224 00:10:05,760 --> 00:10:07,160 TO PRESS BY THREE DAYS. 225 00:10:07,160 --> 00:10:07,440 [LAUGHTER] 226 00:10:07,440 --> 00:10:09,560 OF COURSE, HE WILL NEVER LET ME 227 00:10:09,560 --> 00:10:14,280 FORGET HIS PAPER WAS IN THE NEW 228 00:10:14,280 --> 00:10:17,360 ENGLAND JOURNAL THANK YOU FOR 229 00:10:17,360 --> 00:10:20,000 YOUR GREAT LEADERSHIP AND 230 00:10:20,000 --> 00:10:20,880 URGENCY, CRYSTAL. 231 00:10:20,880 --> 00:10:22,280 AVERY WAS THE FIRST CHILD 232 00:10:22,280 --> 00:10:24,560 TREATED WITH CAR T CELLS IN THE 233 00:10:24,560 --> 00:10:25,560 POB. 234 00:10:25,560 --> 00:10:27,360 HE WAS A BRAVE PIONEER, HAVING 235 00:10:27,360 --> 00:10:32,160 BEEN ONE OF THE FIRST PATIENTS 236 00:10:32,160 --> 00:10:34,880 TREATED ON OUR HA-22, DENDRITIC 237 00:10:34,880 --> 00:10:35,960 CELL VACCINE AND MARKIBO TRIALS. 238 00:10:35,960 --> 00:10:37,600 I PAUSE FOR A MOMENT TO REMEMBER 239 00:10:37,600 --> 00:10:39,440 HIM AND MANY OTHER CHILDREN AND 240 00:10:39,440 --> 00:10:40,640 THEIR FAMILIES WHO HAVE 241 00:10:40,640 --> 00:10:42,760 PARTNERED WITH US OVER THE YEARS 242 00:10:42,760 --> 00:10:45,440 IN OUR WORK AND CONTINUE TO DO 243 00:10:45,440 --> 00:10:47,280 SO. 244 00:10:47,280 --> 00:10:48,680 THE POB RESEARCH TEAM REMAINS 245 00:10:48,680 --> 00:10:51,200 ONE OF THE FINEST I'VE EVER BEEN 246 00:10:51,200 --> 00:10:52,160 ASSOCIATED WITH. 247 00:10:52,160 --> 00:10:53,760 IN ADDITION TO THE INDIVIDUALS 248 00:10:53,760 --> 00:10:55,320 I'VE MENTIONED, I WANT TO 249 00:10:55,320 --> 00:10:56,680 ACKNOWLEDGE OTHER KEY TEAM 250 00:10:56,680 --> 00:10:59,960 MEMBERS OF THE EARLY CAR T 251 00:10:59,960 --> 00:11:01,240 PROGRAM. 252 00:11:01,240 --> 00:11:04,760 RESEARCH NURSES, KELLY RICHARDS, 253 00:11:04,760 --> 00:11:06,760 PAULA LAYTON, CINDY DEL BROOK. 254 00:11:06,760 --> 00:11:08,360 WHO DOESN'T LOVE CINDY? 255 00:11:08,360 --> 00:11:16,960 DATA MANAGEMENT TEAM, KEITH 256 00:11:16,960 --> 00:11:18,880 O'NEIL, LEON, SHALRY AND 257 00:11:18,880 --> 00:11:19,160 EKATERINA. 258 00:11:19,160 --> 00:11:21,000 WITH A PAUSE TO REMEMBER LEON, 259 00:11:21,000 --> 00:11:24,280 WHO SADLY PASSED AWAY FROM 260 00:11:24,280 --> 00:11:25,800 GLIOBLASTOMA WHILE THE EARLY 261 00:11:25,800 --> 00:11:29,320 TEAM WAS ASSEMBLED AT THE POB. 262 00:11:29,320 --> 00:11:32,360 WE RECEIVED GREAT SUPPORT FROM 263 00:11:32,360 --> 00:11:33,920 SHARON, VICKIE RICHMOND AND 264 00:11:33,920 --> 00:11:34,560 OTHERS. 265 00:11:34,560 --> 00:11:36,000 WE HAD FANTASTIC COLLABORATING 266 00:11:36,000 --> 00:11:39,280 COLLEAGUES AND TEAMS ACROSS THE 267 00:11:39,280 --> 00:11:41,440 INTRAMURAL NIH. 268 00:11:41,440 --> 00:11:43,840 CRYSTAL TREY AND I HAD 269 00:11:43,840 --> 00:11:49,800 COLLEAGUES IN TERRY, CHRISTIAN, 270 00:11:49,800 --> 00:11:51,440 JASON, RUMA, AND NIRALI WHO 271 00:11:51,440 --> 00:11:52,880 JOINED IN 2009. 272 00:11:52,880 --> 00:11:54,600 NIRALI CONVINCED ME TO ALLOW HER 273 00:11:54,600 --> 00:11:56,920 TO FORGO LABORATORY TRAINING TO 274 00:11:56,920 --> 00:11:57,640 PURSUE CLINICAL RESEARCH. 275 00:11:57,640 --> 00:11:59,520 THAT MAY HAVE BEEN THE BEST 276 00:11:59,520 --> 00:12:03,360 DECISION I WAS EVER FORCED INTO. 277 00:12:03,360 --> 00:12:07,400 FROM A KNOCK ON THE DOOR, TO A 278 00:12:07,400 --> 00:12:09,040 DECADE OF PARADIGM-CHANGING 279 00:12:09,040 --> 00:12:09,600 CLINICAL DEVELOPMENTS, 280 00:12:09,600 --> 00:12:10,800 CONGRATULATIONS TO EVERYONE 281 00:12:10,800 --> 00:12:14,400 INVOLVED IN THIS REMARKABLE 282 00:12:14,400 --> 00:12:15,400 PROGRESS. 283 00:12:15,400 --> 00:12:17,680 ENJOY THIS WELL-DESERVED 284 00:12:17,680 --> 00:12:19,440 CELEBRATION. 285 00:12:19,440 --> 00:12:23,880 [APPLAUSE] 286 00:12:23,880 --> 00:12:25,360 WE'LL HAVE ONE MORE VIDEO, 287 00:12:25,360 --> 00:12:25,800 >>HI, EVERYONE. 288 00:12:25,800 --> 00:12:27,960 I WISH I COULD BE THERE WITH YOU 289 00:12:27,960 --> 00:12:32,760 AND I MISS YOU ALL TO CELEBRATE 290 00:12:32,760 --> 00:12:34,640 THIS OCCASION OF CELEBRATING ALL 291 00:12:34,640 --> 00:12:36,800 OF THE TREMENDOUS WORK THAT'S 292 00:12:36,800 --> 00:12:38,480 BEEN DONE IN THE PEDIATRIC 293 00:12:38,480 --> 00:12:40,320 ONCOLOGY BRANCH. 294 00:12:40,320 --> 00:12:41,520 WHAT HAS BECOME A TRANSFORMATIVE 295 00:12:41,520 --> 00:12:43,720 FIELD IN THE TREATMENT OF 296 00:12:43,720 --> 00:12:44,440 PATIENTS. 297 00:12:44,440 --> 00:12:47,480 YOU KNOW, WHEN I REFLECT BACK ON 298 00:12:47,480 --> 00:12:49,400 MY TIME IN THE PEDIATRIC 299 00:12:49,400 --> 00:12:51,760 ONCOLOGY BRANCH, I THINK OF IT 300 00:12:51,760 --> 00:12:56,600 AS THE TIME IN MY CAREER WHEN -- 301 00:12:56,600 --> 00:13:01,000 THAT I CAN BE MOST PROUD OF. 302 00:13:01,000 --> 00:13:04,400 I REMEMBER, YOU KNOW, THE EARLY 303 00:13:04,400 --> 00:13:08,080 DAYS OF THE CD19 AND CD22 CAR T 304 00:13:08,080 --> 00:13:09,200 CELL PROGRAMS. 305 00:13:09,200 --> 00:13:13,920 YOU KNOW, VERY SPECIFIC MEMORIES 306 00:13:13,920 --> 00:13:17,120 AROUND, YOU KNOW, AN INTERACTION 307 00:13:17,120 --> 00:13:19,280 WITH THE DNA RECOMBINANT 308 00:13:19,280 --> 00:13:21,160 ADVISORY COMMITTEE THAT WAS NOT 309 00:13:21,160 --> 00:13:24,320 ONE OF MY SHINING MOMENTS THAT 310 00:13:24,320 --> 00:13:28,800 PROMPTED ME TO TURN MY MY BACK 311 00:13:28,800 --> 00:13:32,520 ON THE COMMITTEE IN FRUSTRATION 312 00:13:32,520 --> 00:13:34,040 BUT ULTIMATELY FORTUNATELY 313 00:13:34,040 --> 00:13:35,800 DIDN'T RESULT US IN US BEING 314 00:13:35,800 --> 00:13:38,440 ABLE TO OPEN THE TRIAL. 315 00:13:38,440 --> 00:13:40,320 I REMEMBER THE FIRST 316 00:13:40,320 --> 00:13:42,520 MANUFACTURING OF THE CD22 CAR 317 00:13:42,520 --> 00:13:46,320 PRODUCTS WHICH WAS THE FIRST 318 00:13:46,320 --> 00:13:47,640 LENTIVIRAL MANUFACTURING PROCESS 319 00:13:47,640 --> 00:13:49,720 WITHIN THE CELL PROCESSING 320 00:13:49,720 --> 00:13:50,160 SECTION. 321 00:13:50,160 --> 00:13:54,640 AND, YOU KNOW, ON DAY 5 OF 322 00:13:54,640 --> 00:13:55,240 MANUFACTURING, NEEDING TO MAKE 323 00:13:55,240 --> 00:14:01,760 DECISIONS WHETHER WE WERE GOING 324 00:14:01,760 --> 00:14:03,840 TO START CHEMOTHERAPY, AND THE 325 00:14:03,840 --> 00:14:05,680 CELLS LOOKED TERRIBLE ON THAT 326 00:14:05,680 --> 00:14:05,840 DAY. 327 00:14:05,840 --> 00:14:07,360 I REMEMBER A LOT OF OF ANGST 328 00:14:07,360 --> 00:14:14,480 OVER THE WEEKEND AFTER WE MADE 329 00:14:14,480 --> 00:14:18,960 DECISIONS TO START PREPAREATIVE 330 00:14:18,960 --> 00:14:19,400 CHEMOTHERAPY. 331 00:14:19,400 --> 00:14:20,320 I REMEMBER COLLABORATION BETWEEN 332 00:14:20,320 --> 00:14:22,240 MEMBERS OF THE TEAM. 333 00:14:22,240 --> 00:14:23,400 I REMEMBER SPEAKING DIRECTLY 334 00:14:23,400 --> 00:14:25,320 WITH ALL OF THE TECHNICIANS IN 335 00:14:25,320 --> 00:14:26,720 THE CELL PROCESSING SECTION WHO 336 00:14:26,720 --> 00:14:32,640 WOULD CALL ME DURING THE EARLY 337 00:14:32,640 --> 00:14:33,600 MANUFACTURING PROCESSES, I 338 00:14:33,600 --> 00:14:35,160 REMEMBER SITTING DOWN WITH THE 339 00:14:35,160 --> 00:14:36,880 FLOW CYTOMETRY GROUP TO REVIEW 340 00:14:36,880 --> 00:14:37,120 DATA. 341 00:14:37,120 --> 00:14:38,720 I REMEMBER WORKING WITH THE 342 00:14:38,720 --> 00:14:40,840 NURSES ON THE UNIT. 343 00:14:40,840 --> 00:14:44,040 I REMEMBER THE TERRIFIC WORK OF 344 00:14:44,040 --> 00:14:45,120 THE RESEARCH NURSES, YOU KNOW, 345 00:14:45,120 --> 00:14:48,080 TO GET THESE PATIENTS ENROLLED 346 00:14:48,080 --> 00:14:49,400 ON TRIALS. 347 00:14:49,400 --> 00:14:53,240 YOU KNOW, BUT MOSTLY, YOU KNOW, 348 00:14:53,240 --> 00:14:56,920 WHAT I REMEMBER ARE THE PATIENTS 349 00:14:56,920 --> 00:15:00,000 THAT BENEFITED FROM ALL OF THE 350 00:15:00,000 --> 00:15:02,880 TREMENDOUS WORK THAT WENT ON IN 351 00:15:02,880 --> 00:15:05,040 THE PEDIATRIC ONCOLOGY BRANCH. 352 00:15:05,040 --> 00:15:07,880 AND MAYBE EVEN MORE IMPORTANTLY, 353 00:15:07,880 --> 00:15:10,400 I REMEMBER THE PATIENTS THAT 354 00:15:10,400 --> 00:15:12,440 PROMPT US TO WANT TO DO BETTER. 355 00:15:12,440 --> 00:15:13,920 SO, I WISH I COULD THERE BE WITH 356 00:15:13,920 --> 00:15:15,120 ALL OF YOU. 357 00:15:15,120 --> 00:15:16,400 I LOVE YOU ALL. 358 00:15:16,400 --> 00:15:18,920 AND THANK YOU FOR GIVING ME AN 359 00:15:18,920 --> 00:15:19,880 OPPORTUNITY TO SHARE MY 360 00:15:19,880 --> 00:15:22,880 THOUGHTS. 361 00:15:22,880 --> 00:15:27,960 [APPLAUSE] 362 00:15:27,960 --> 00:15:28,800 WELL, THANK YOU, EVERYONE, FOR 363 00:15:28,800 --> 00:15:29,600 BEING HERE. 364 00:15:29,600 --> 00:15:31,480 IT IS REALLY JUST SUCH A 365 00:15:31,480 --> 00:15:33,920 PLEASURE AND HONOR AND TRULY A 366 00:15:33,920 --> 00:15:34,200 PRIVILEGE. 367 00:15:34,200 --> 00:15:36,200 WHAT I WANT TO START OFF BY 368 00:15:36,200 --> 00:15:37,720 SAYING IS ACTUALLY THE 369 00:15:37,720 --> 00:15:38,080 ACKNOWLEDGMENTS. 370 00:15:38,080 --> 00:15:39,360 OFTEN WE DON'T MAKE TIME TO GET 371 00:15:39,360 --> 00:15:41,320 TO THESE TILL THE END BUT TODAY 372 00:15:41,320 --> 00:15:44,280 WE HAVE TO SPEND TIME AND THANK 373 00:15:44,280 --> 00:15:44,560 EVERYBODY. 374 00:15:44,560 --> 00:15:46,920 TO KNOW THIS WORK COULD NOT BE 375 00:15:46,920 --> 00:15:48,680 DONE WITHOUT YOU. 376 00:15:48,680 --> 00:15:50,640 THAT INCLUDES OUR CONSULTING 377 00:15:50,640 --> 00:15:53,600 COLLEAGUES, THOSE FROM CCMD IN 378 00:15:53,600 --> 00:15:56,120 THE ICU, DEPARTMENT OF 379 00:15:56,120 --> 00:15:57,440 TRANSFUSION MEDICINE, NURSING, 380 00:15:57,440 --> 00:15:59,440 BEDSIDE NURSES AND RESEARCH 381 00:15:59,440 --> 00:16:01,040 NURSES, TRAINEES, TWO OF THEM 382 00:16:01,040 --> 00:16:02,840 WHO WENT OUT OF THEIR WAY TODAY 383 00:16:02,840 --> 00:16:04,160 TO MAKE COOKIES AND A CAKE FOR A 384 00:16:04,160 --> 00:16:06,280 PATIENT OF OURS WHO IS 385 00:16:06,280 --> 00:16:09,000 CELEBRATING A BIRTHDAY TODAY. 386 00:16:09,000 --> 00:16:10,800 OUR TEACHERS, TECH TRANSFER 387 00:16:10,800 --> 00:16:13,400 TEAMS, ALL OF CCR AND LEADERSHIP 388 00:16:13,400 --> 00:16:14,480 WHO SUPPORTED THE CAR T CELL 389 00:16:14,480 --> 00:16:17,240 PROGRAMS ALONG THE WAY. 390 00:16:17,240 --> 00:16:18,360 THE CHILDREN'S INN, A PARTNER IN 391 00:16:18,360 --> 00:16:22,280 ALL OF THE WORK WE DO, REFERRING 392 00:16:22,280 --> 00:16:24,520 TEAMS WHERE PATIENTS COME FROM, 393 00:16:24,520 --> 00:16:26,320 FLOW CYTOMETRY TEAMS, TEAMS IN 394 00:16:26,320 --> 00:16:27,680 FREDERICK FOR SUPPORTING CAR T 395 00:16:27,680 --> 00:16:30,640 CELL PROGRAMS AS WELL, THOSE IN 396 00:16:30,640 --> 00:16:34,680 CENTER FOR CELLULAR ENGINEERING, 397 00:16:34,680 --> 00:16:35,320 INTERVENTIONAL RADIOLOGISTS, 398 00:16:35,320 --> 00:16:38,520 WITHOUT WHOM WE COULDN'T DO 399 00:16:38,520 --> 00:16:40,000 APHERESIS, THERAPISTS, 400 00:16:40,000 --> 00:16:41,600 PSYCHOLOGISTS, FOLKSES IN ART 401 00:16:41,600 --> 00:16:42,200 AND REC THERAPY. 402 00:16:42,200 --> 00:16:47,920 IF YOU TRIED TO DO AN APHERESIS 403 00:16:47,920 --> 00:16:49,320 ON A 5-YEAR-OLD YOU NEED MORE 404 00:16:49,320 --> 00:16:50,480 THAN SCIENCE, YOU NEED SOMEONE 405 00:16:50,480 --> 00:16:51,360 WITH THE CHILDREN. 406 00:16:51,360 --> 00:16:52,520 WE'RE GRATEFUL FOR EVERYTHING 407 00:16:52,520 --> 00:16:55,120 YOU DO. 408 00:16:55,120 --> 00:16:57,440 OUR DATA MANAGERS WERE BRIEFLY 409 00:16:57,440 --> 00:16:59,960 MENTIONED BUT WE HAVE PROBABLY 410 00:16:59,960 --> 00:17:01,360 THE MOST WELL ESTABLISHED DATA 411 00:17:01,360 --> 00:17:03,320 MANAGERS IN THE CAR T CELL FIELD 412 00:17:03,320 --> 00:17:04,120 IN OUR GROUP. 413 00:17:04,120 --> 00:17:06,520 WE'VE BEEN ABLE TO KEEP THEM 414 00:17:06,520 --> 00:17:07,120 HERE. 415 00:17:07,120 --> 00:17:08,200 IT'S JUST A TREMENDOUS TESTAMENT 416 00:17:08,200 --> 00:17:10,240 TO WHAT THEY DO FOR US. 417 00:17:10,240 --> 00:17:12,440 SO, THIS WORK COULD NOT BE DONE 418 00:17:12,440 --> 00:17:13,400 WITHOUT YOU. 419 00:17:13,400 --> 00:17:14,600 SO THANK YOU. 420 00:17:14,600 --> 00:17:17,240 I THINK WITH THE CAR T CELL 421 00:17:17,240 --> 00:17:19,880 PROGRAM AND PEDIATRIC ONCOLOGY 422 00:17:19,880 --> 00:17:22,520 BRANCH REPRESENTING TRULY THE 423 00:17:22,520 --> 00:17:24,440 EPITOME OF TEAM SCIENCE. 424 00:17:24,440 --> 00:17:27,360 AT THE CORE, HOWEVER, IS OUR 425 00:17:27,360 --> 00:17:28,080 PATIENTS AND OUR FAMILIES. 426 00:17:28,080 --> 00:17:30,680 SHOWN HERE IN THE TOP LEFT 427 00:17:30,680 --> 00:17:32,440 CORNER, HE ALWAYS RESPONDS AS 428 00:17:32,440 --> 00:17:39,920 AVERY WITH DR. WAYNE, WE'LL HEAR 429 00:17:39,920 --> 00:17:45,160 FROM TRISH DALEY, AVERY'S MOM, 430 00:17:45,160 --> 00:17:46,320 OUR FIRST PATIENT TREATED A YEAR 431 00:17:46,320 --> 00:17:48,000 AGO ON HIS BIRTHDAY. 432 00:17:48,000 --> 00:17:49,120 TODAY WE'LL CELEBRATE ANOTHER 433 00:17:49,120 --> 00:17:50,800 BIRTHDAY AND ANOTHER CAR 434 00:17:50,800 --> 00:17:51,520 INFUSION. 435 00:17:51,520 --> 00:17:52,960 IT TELLS YOU WE'VE REALLY COME 436 00:17:52,960 --> 00:17:54,240 FULL CIRCLE IN WHERE WE ARE, 437 00:17:54,240 --> 00:17:58,200 CAN'T WAIT TO SEE WHAT THE 438 00:17:58,200 --> 00:17:59,440 FUTURE WILL BRING. 439 00:17:59,440 --> 00:18:01,160 OUR PATIENTS TRAVEL THE WORLD TO 440 00:18:01,160 --> 00:18:04,080 COME HERE, SHOWN HERE IS OUR 441 00:18:04,080 --> 00:18:05,880 DEMOGRAPHICS OF -- IT'S ALREADY 442 00:18:05,880 --> 00:18:07,640 OUTDATED BUT YOU CAN SEE WHERE 443 00:18:07,640 --> 00:18:08,600 PATIENTS COME FROM. 444 00:18:08,600 --> 00:18:10,240 THEY REALLY DO SOME HERE FROM 445 00:18:10,240 --> 00:18:14,120 ALL OVER THE WORLD, BUT A THIRD 446 00:18:14,120 --> 00:18:15,600 OF PATIENTS BEING INTERNATIONAL. 447 00:18:15,600 --> 00:18:17,800 TO BE HERE AT WHAT FRANCIS 448 00:18:17,800 --> 00:18:20,080 COLLINS CALLED THE NATIONAL 449 00:18:20,080 --> 00:18:20,840 INSTITUTES OF HOPE. 450 00:18:20,840 --> 00:18:22,880 AND WHO ARE THE PATIENTS WHO 451 00:18:22,880 --> 00:18:24,440 COME TO THE NIH? 452 00:18:24,440 --> 00:18:27,200 THEY ARE PATIENTS WITH RELAPSE 453 00:18:27,200 --> 00:18:28,360 OR REFRACTORY DISEASE, 454 00:18:28,360 --> 00:18:30,600 ESPECIALLY WITH PEDIATRIC B CELL 455 00:18:30,600 --> 00:18:33,560 ALL, MAY HAVE BEEN STANDARD RISK 456 00:18:33,560 --> 00:18:37,280 UP FRONT AT DIAGNOSIS, WITH 457 00:18:37,280 --> 00:18:40,960 CURATIVE INTENT SOMEHOW ALONG 458 00:18:40,960 --> 00:18:42,200 THE WAY THE TREATMENT APPROACHES 459 00:18:42,200 --> 00:18:44,520 FAILED AND THEY HAD TO FIND 460 00:18:44,520 --> 00:18:45,600 ALTERNATIVE OPTIONS. 461 00:18:45,600 --> 00:18:47,320 THE PATIENTS WHO COME HERE ARE 462 00:18:47,320 --> 00:18:49,200 THOSE FOR WHOM STANDARD 463 00:18:49,200 --> 00:18:50,760 THERAPIES HAVE FAILED. 464 00:18:50,760 --> 00:18:52,280 INITIALLY IT WAS JUST 465 00:18:52,280 --> 00:18:53,920 CHEMOTHERAPY OR STEM CELL 466 00:18:53,920 --> 00:18:55,160 TRANSPLANT. 467 00:18:55,160 --> 00:18:57,840 BUT OVER THE YEARS WE'VE HAD 468 00:18:57,840 --> 00:19:00,360 PATIENTS FOR WHOM IMMUNOTHERAPY 469 00:19:00,360 --> 00:19:00,720 FAILS. 470 00:19:00,720 --> 00:19:02,800 HOW WE KNOW OUR PATIENTS AND 471 00:19:02,800 --> 00:19:06,520 FAMILIES IS THEY ARE CHILDREN, 472 00:19:06,520 --> 00:19:10,680 WHO LOVE TO DANCE. 473 00:19:10,680 --> 00:19:12,080 PLAY LEGOS, AND SING. 474 00:19:12,080 --> 00:19:14,520 THEY ARE TEENS WHO WANT TO GO ON 475 00:19:14,520 --> 00:19:15,680 A SHOPPING SPREE, LOVING 476 00:19:15,680 --> 00:19:17,000 BROTHERS AND SISTERS. 477 00:19:17,000 --> 00:19:18,720 THEY ARE STUDENTS WHO BELIEVE IT 478 00:19:18,720 --> 00:19:22,160 OR NOT ARE TAKING THEIR FINAL 479 00:19:22,160 --> 00:19:23,480 EXAMS DURING CYTOKINE RELEASE 480 00:19:23,480 --> 00:19:23,880 SYNDROME. 481 00:19:23,880 --> 00:19:25,880 YOU THINK, YOU HAVE A FEVER TO 482 00:19:25,880 --> 00:19:28,000 104, I THINK I CAN GIVE YOU AN 483 00:19:28,000 --> 00:19:28,240 EXCUSE. 484 00:19:28,240 --> 00:19:29,800 THEY ARE GOING TO FINISH THOSE 485 00:19:29,800 --> 00:19:33,080 FINAL EXAMS, BELIEVE IT OR NOT. 486 00:19:33,080 --> 00:19:39,000 THE OTHER DAY I SAID TO MY TEAM, 487 00:19:39,000 --> 00:19:41,240 HE'S FINE, HE'S JUST CODING. 488 00:19:41,240 --> 00:19:43,280 I REALIZED I SHOULD HAVE 489 00:19:43,280 --> 00:19:45,080 PREFACED HE WAS DOING HIS 490 00:19:45,080 --> 00:19:46,560 COMPUTER PROGRAMMING. 491 00:19:46,560 --> 00:19:49,760 CODING IN A CLINTON CENTER IS 492 00:19:49,760 --> 00:19:50,360 NOT VIEWED FAVORABLY. 493 00:19:50,360 --> 00:19:50,920 [LAUGHTER] 494 00:19:50,920 --> 00:19:51,720 I LEARNED MY LESSON. 495 00:19:51,720 --> 00:19:53,920 THIS IS WHAT OUR PATIENTS ARE 496 00:19:53,920 --> 00:19:55,760 DOING WHILE GETTING INFUSIONS, 497 00:19:55,760 --> 00:19:57,160 WHILE THEY ARE HERE DOING 498 00:19:57,160 --> 00:19:59,000 EVERYTHING TO MAINTAIN A SENSE 499 00:19:59,000 --> 00:20:00,120 OF NORMALCY. 500 00:20:00,120 --> 00:20:01,440 I CANNOT BEGIN TO THANK YOU, ALL 501 00:20:01,440 --> 00:20:03,200 OF YOU, FOR EVERYTHING YOU DO TO 502 00:20:03,200 --> 00:20:07,120 MAKE THIS POSSIBLE FOR THEM. 503 00:20:07,120 --> 00:20:09,000 AS WE TREAT ADOLESCENTS AND 504 00:20:09,000 --> 00:20:10,560 YOUNG ADULTS PATIENTS MAY HAVE 505 00:20:10,560 --> 00:20:13,160 CHILDREN OF THEIR OWN. 506 00:20:13,160 --> 00:20:16,760 THEY ARE PARENTS AND THEY ARE 507 00:20:16,760 --> 00:20:17,760 SPOUSES. 508 00:20:17,760 --> 00:20:20,040 AND OUR PATIENTS ARE LOVED AND 509 00:20:20,040 --> 00:20:21,480 THEY HAVE HOPES AND THEY HAVE 510 00:20:21,480 --> 00:20:21,800 DREAMS. 511 00:20:21,800 --> 00:20:24,000 AND IT IS SUCH A PRIVILEGE AND 512 00:20:24,000 --> 00:20:26,080 HONOR TO BE EVEN A SMALL PART OF 513 00:20:26,080 --> 00:20:28,040 THEIR JOURNEY TO KNOW WE HAVE 514 00:20:28,040 --> 00:20:29,360 CONTRIBUTED THAT IN SOME WAY. 515 00:20:29,360 --> 00:20:31,560 AND I HOPE THAT WHAT I CAN SHOW 516 00:20:31,560 --> 00:20:32,720 YOU IS HOW MEANINGFUL THE 517 00:20:32,720 --> 00:20:34,200 PROGRAM IS BECAUSE OF THE PEOPLE 518 00:20:34,200 --> 00:20:38,120 WE SERVE AND PATIENTS WHO ARE 519 00:20:38,120 --> 00:20:38,400 HERE. 520 00:20:38,400 --> 00:20:40,600 TODAY IS TEN YEARS SINCE THE 521 00:20:40,600 --> 00:20:42,840 FIRST POB CAR T CELL INFUSION. 522 00:20:42,840 --> 00:20:44,120 YOU WILL HEAR, YOU HAVE HEARD A 523 00:20:44,120 --> 00:20:45,440 LITTLE BIT ABOUT OUR HISTORY AND 524 00:20:45,440 --> 00:20:47,640 HOW OUR PROGRAM CAME TO BE. 525 00:20:47,640 --> 00:20:49,400 WE'LL TALK ABOUT OUR 526 00:20:49,400 --> 00:20:50,160 ADVANCEMENTS AND ACHIEVEMENTS 527 00:20:50,160 --> 00:20:54,440 OVER THIS TIME AS WELL AS FUTURE 528 00:20:54,440 --> 00:20:54,720 DIRECTIONS. 529 00:20:54,720 --> 00:20:56,520 MORE IMPORTANTLY, YOU'LL HEAR 530 00:20:56,520 --> 00:20:58,080 EXPERIENCES WITH PATIENTS ANDS 531 00:20:58,080 --> 00:20:59,480 FAMILIES AND LOVED ONES. 532 00:20:59,480 --> 00:21:00,680 I'M GRATEFUL FOR FAMILIES HERE 533 00:21:00,680 --> 00:21:02,240 ON SITE AND LOOK FORWARD TO 534 00:21:02,240 --> 00:21:02,960 INTRODUCING YOU. 535 00:21:02,960 --> 00:21:04,320 WE'LL HAVE A FEW VIDEOS THAT 536 00:21:04,320 --> 00:21:05,480 I'LL SHARE FROM THOSE WHO 537 00:21:05,480 --> 00:21:07,680 COULDN'T MAKE IT BUT REALLY 538 00:21:07,680 --> 00:21:11,840 WANTED TO BE HERE AS WELL AS 539 00:21:11,840 --> 00:21:13,040 NOTES LATER TODAY. 540 00:21:13,040 --> 00:21:14,480 WHILE WE CELEBRATE THOSE 541 00:21:14,480 --> 00:21:16,560 ACHIEVEMENTS, TODAY IS ALSO A 542 00:21:16,560 --> 00:21:17,440 TIME TO REFLECT. 543 00:21:17,440 --> 00:21:19,200 IT IS TIME TO REFLECT ON THOSE 544 00:21:19,200 --> 00:21:21,800 WHO ARE CURED AND HAVE THE HEY 545 00:21:21,800 --> 00:21:22,600 BUILT TO BECOME LONG-TERM 546 00:21:22,600 --> 00:21:24,080 SURVIVORS AND WE'RE SO GRATEFUL 547 00:21:24,080 --> 00:21:27,480 WE SHARE EACH DAY IN YOUR 548 00:21:27,480 --> 00:21:29,280 HAPPINESS. 549 00:21:29,280 --> 00:21:31,120 TIME TO REFLECT ON THOSE STILL 550 00:21:31,120 --> 00:21:33,520 RECEIVING THERAPY WHERE CAR MAY 551 00:21:33,520 --> 00:21:34,720 NOT HAVE OPTIMALLY WORKED, OR 552 00:21:34,720 --> 00:21:37,240 THOSE STARTING THE JOURNEY WITH 553 00:21:37,240 --> 00:21:38,360 US, NOT SURE WHAT THE CRYSTAL 554 00:21:38,360 --> 00:21:41,760 BALANCE WILL -- BALL WITHHOLD. 555 00:21:41,760 --> 00:21:46,120 FOR THOSE NO LONGER WITH US, I 556 00:21:46,120 --> 00:21:48,320 HOPE YOU SEE HOW WE STRIVE TO 557 00:21:48,320 --> 00:21:49,960 KEEP THEIR MEMORIES ALIVE AND 558 00:21:49,960 --> 00:21:52,840 PRESERVE THE LEGACY THAT THEY 559 00:21:52,840 --> 00:21:54,200 HAVE HONORED US WITH. 560 00:21:54,200 --> 00:21:55,680 AND WITH THAT, I'D LIKE TO TAKE 561 00:21:55,680 --> 00:21:59,160 A MOMENT OF SILENCE TO REFLECT 562 00:21:59,160 --> 00:22:00,840 ON ALL THE FAMILIES WHO COME 563 00:22:00,840 --> 00:22:08,840 HERE THROUGH THE NIH. 564 00:22:08,840 --> 00:22:10,360 I'D NOW LIKE TO TAKE THIS 565 00:22:10,360 --> 00:22:12,200 OPPORTUNITY TO TALK ABOUT OUR 566 00:22:12,200 --> 00:22:14,560 CAR T CELL PROGRAM AND PRIDE AND 567 00:22:14,560 --> 00:22:15,800 JOY THAT IT IS. 568 00:22:15,800 --> 00:22:17,440 SHOWN HERE IS HOW OUR SECTION IS 569 00:22:17,440 --> 00:22:18,320 LINED UP. 570 00:22:18,320 --> 00:22:20,520 WE HAVE OUR PATIENTS WHO COME TO 571 00:22:20,520 --> 00:22:22,840 US FROM THE REFERRING CENTERS. 572 00:22:22,840 --> 00:22:24,360 THEY COME TO THE CLINICAL 573 00:22:24,360 --> 00:22:24,600 CENTER. 574 00:22:24,600 --> 00:22:26,440 AGAIN, THE PATIENTS WHO COME 575 00:22:26,440 --> 00:22:28,640 HERE ARE THOSE FOR WHOM STANDARD 576 00:22:28,640 --> 00:22:30,040 THERAPIES FAILED, WE'RE STRIVING 577 00:22:30,040 --> 00:22:35,440 TO FIND WAYS TO IMPROVE UPON 578 00:22:35,440 --> 00:22:36,040 THOSE THERAPIES AND ERADICATE 579 00:22:36,040 --> 00:22:36,480 DISEASE. 580 00:22:36,480 --> 00:22:38,440 EVERY PART OF THE PROCESS FROM 581 00:22:38,440 --> 00:22:42,480 EVALUATION TO T CELL COLLECTION 582 00:22:42,480 --> 00:22:43,200 TO OPTIMIZING APHERESIS AND CAR 583 00:22:43,200 --> 00:22:45,480 T CELL MANUFACTURING TO THE 584 00:22:45,480 --> 00:22:48,400 INFUSIONS PRIMARILY STILL DONE 585 00:22:48,400 --> 00:22:50,600 AS INPATIENT, INCLUDING THE VERY 586 00:22:50,600 --> 00:22:54,160 CLOSE AND EXTENSIVE MONITORING 587 00:22:54,160 --> 00:22:56,320 TOXICITY MANAGEMENT AND RESPONSE 588 00:22:56,320 --> 00:22:57,960 TO TERMINATION IS ALL DONE HERE 589 00:22:57,960 --> 00:23:01,720 AS PART OF THE PROCESS FOR 590 00:23:01,720 --> 00:23:04,280 PATIENT AND THEIR JOURNEY. 591 00:23:04,280 --> 00:23:06,480 WE HAVE EXTENSIVE STUDIES 592 00:23:06,480 --> 00:23:07,280 THROUGH MANY COLLABORATIONS, 593 00:23:07,280 --> 00:23:09,760 LATER TODAY YOU'LL HEAR FROM 594 00:23:09,760 --> 00:23:10,720 MANY COLLEAGUES, THE 595 00:23:10,720 --> 00:23:12,320 EXTRAORDINARY WORK THAT HAS BEEN 596 00:23:12,320 --> 00:23:13,840 DONE OVER THIS PAST DECADE, 597 00:23:13,840 --> 00:23:16,360 YOU'LL HEAR ABOUT WHAT THINGS 598 00:23:16,360 --> 00:23:18,080 ARE FORTHCOMING. 599 00:23:18,080 --> 00:23:18,560 THAT INCLUDES CYTOKINE 600 00:23:18,560 --> 00:23:20,920 PROFILING, LOOKING AT WHERE THE 601 00:23:20,920 --> 00:23:23,800 CAR T CELLS GO, AT THE 602 00:23:23,800 --> 00:23:24,640 TOXICITIES AND RESPONSE, TRYING 603 00:23:24,640 --> 00:23:28,160 TO IMPROVE UPON THEM SO PATIENTS 604 00:23:28,160 --> 00:23:29,440 CAN TOLERATE THERAPY AND COME 605 00:23:29,440 --> 00:23:32,720 OUT EVEN BETTER OFF THAN WHERE 606 00:23:32,720 --> 00:23:35,160 THEY STARTED BEFORE RECEIVING 607 00:23:35,160 --> 00:23:35,920 IT. 608 00:23:35,920 --> 00:23:37,040 PATIENTS ARE EVALUATED FOR 609 00:23:37,040 --> 00:23:38,440 LEUKEMIA BIOLOGY AND WE'RE SO 610 00:23:38,440 --> 00:23:44,520 GRATEFUL TO BE PARTNERED WITH 611 00:23:44,520 --> 00:23:46,760 THE FLOW CYTOMETRY TEAM. 612 00:23:46,760 --> 00:23:48,600 LEUKEMIA CELLS, AS THEY TARGET 613 00:23:48,600 --> 00:23:51,760 PROTEINS THAT MAY GO AWAY OVER 614 00:23:51,760 --> 00:23:53,200 TIME. 615 00:23:53,200 --> 00:23:56,920 WE'RE DOING EVALUATIONS OF CAR T 616 00:23:56,920 --> 00:23:58,000 CELL CHARACTERIZATION, I'M 617 00:23:58,000 --> 00:24:00,440 GRATEFUL TO CENTER FOR CELLULAR 618 00:24:00,440 --> 00:24:03,360 ENGINEERING, UNDER DAVE AND NEW 619 00:24:03,360 --> 00:24:04,920 COLLABORATIONS WITH DR. TAYLOR, 620 00:24:04,920 --> 00:24:06,000 AS THEY INTERROGATE THOSE 621 00:24:06,000 --> 00:24:07,880 PRODUCTS AND LEARN MORE FROM 622 00:24:07,880 --> 00:24:09,160 THEM. 623 00:24:09,160 --> 00:24:10,480 ULTIMATELY WE'RE TRYING TO 624 00:24:10,480 --> 00:24:13,640 OPTIMIZE STRATEGIES IN EVERY 625 00:24:13,640 --> 00:24:14,040 CAPACITY POSSIBLE. 626 00:24:14,040 --> 00:24:16,560 OVER THE YEARS YOU CAN SEE WE 627 00:24:16,560 --> 00:24:19,000 STARTED THE CD19 CAR T CELL 628 00:24:19,000 --> 00:24:23,080 PROGRAM IN 2012, OUR FIRST 629 00:24:23,080 --> 00:24:23,360 INFUSION. 630 00:24:23,360 --> 00:24:26,120 THE CD22 CAR T CELL TRIAL WAS 631 00:24:26,120 --> 00:24:29,520 THE SECOND CAR TRIAL IN A-L-L. 632 00:24:29,520 --> 00:24:32,160 WE STARTED TO EMBARK ON SOLID 633 00:24:32,160 --> 00:24:32,680 TUMORS. 634 00:24:32,680 --> 00:24:37,840 YOU'LL HEAR FROM ROSIE KAPLAN 635 00:24:37,840 --> 00:24:39,440 ABOUT GD2 TARGETING AND WHAT THE 636 00:24:39,440 --> 00:24:40,040 FUTURE HOLDS. 637 00:24:40,040 --> 00:24:41,920 YOU CAN SEE THE RATE OF PROGRESS 638 00:24:41,920 --> 00:24:43,840 STARTS TORE PICK UP. 639 00:24:43,840 --> 00:24:48,600 WE HAVE ONE TRIAL IN 2012, ONE 640 00:24:48,600 --> 00:24:54,040 IN 2014, OUR 19 AND 22 STRATEGY 641 00:24:54,040 --> 00:24:57,080 IN 2018, NOW INTO AML, 642 00:24:57,080 --> 00:24:58,280 ALTERNATIVE RARE DISEASES AND 643 00:24:58,280 --> 00:25:00,240 HAVE A NEW TRIAL FORTH COMING. 644 00:25:00,240 --> 00:25:02,600 OVER THIS TIME WE HAVE 645 00:25:02,600 --> 00:25:04,840 ACCUMULATED A DECADE WORD OF 646 00:25:04,840 --> 00:25:08,600 EXPERIENCE IN CHILDREN AND YOUNG 647 00:25:08,600 --> 00:25:09,280 ADULTS. 648 00:25:09,280 --> 00:25:10,640 WE'RE EXTENDING EFFORTS INTO 649 00:25:10,640 --> 00:25:14,400 AML, SOLID TUMORS, RARE 650 00:25:14,400 --> 00:25:15,880 MALIGNANCIES, AND SUPPORTING THE 651 00:25:15,880 --> 00:25:19,680 DEVELOPMENT OF CAR T CELL 652 00:25:19,680 --> 00:25:23,600 PROGRAMS AND SOLID TUMORS ACROSS 653 00:25:23,600 --> 00:25:24,400 PEDIATRIC BRANCH AND CLINICAL 654 00:25:24,400 --> 00:25:25,840 CENTER AS A WHOLE. 655 00:25:25,840 --> 00:25:28,360 IN ITEMS OF CAR T CELL TOXICITY 656 00:25:28,360 --> 00:25:32,280 I WANT TO HIGHLIGHT A FEW 657 00:25:32,280 --> 00:25:34,800 ACHIEVEMENTS RELATED TO 658 00:25:34,800 --> 00:25:39,800 NEUROTOXICITY, INFECTIOUS 659 00:25:39,800 --> 00:25:43,240 COMPLICATIONS, CYTOKINE RELEASE, 660 00:25:43,240 --> 00:25:44,200 OTHER RARE INFLAMMATORY 661 00:25:44,200 --> 00:25:45,640 RESPONSES. 662 00:25:45,640 --> 00:25:46,400 WE'RE LOOKING AT OPTIMIZING CAR 663 00:25:46,400 --> 00:25:48,680 T CELL RESPONSES PANDEMIC IMPACT 664 00:25:48,680 --> 00:25:50,800 OF OTHER FORMS OF IMMUNOTHERAPY, 665 00:25:50,800 --> 00:25:51,680 HOW THEY MAY IMPACT OUTCOMES. 666 00:25:51,680 --> 00:25:53,520 WE LOOK AT WHAT HAPPENS TO 667 00:25:53,520 --> 00:25:55,160 PATIENTS AFTER GETTING A STEM 668 00:25:55,160 --> 00:25:56,280 CELL TRANSPLANT WHEN THEY GET 669 00:25:56,280 --> 00:26:00,240 CAR T CELLS FIRST AND HOW CAN WE 670 00:26:00,240 --> 00:26:02,600 IMPROVE OUTCOMES. 671 00:26:02,600 --> 00:26:03,600 WE'RE THINKING ABOUT 672 00:26:03,600 --> 00:26:04,360 EXTRAMEDULLARY DISEASE. 673 00:26:04,360 --> 00:26:05,920 YOU KNOW WHAT A HUGE PROBLEM 674 00:26:05,920 --> 00:26:09,840 THAT IS AND HOW IT'S 675 00:26:09,840 --> 00:26:10,520 UNDERRECOGNIZED, UNAPPRECIATED, 676 00:26:10,520 --> 00:26:12,240 HOW OUR EFFORTS ARE HELPING SHED 677 00:26:12,240 --> 00:26:15,040 LINE ON THOSE AREAS THAT ARE 678 00:26:15,040 --> 00:26:15,440 UNKNOWN. 679 00:26:15,440 --> 00:26:18,040 HOW TO THINK ABOUT OPTIMIZING 680 00:26:18,040 --> 00:26:18,960 RESPONSE TO SUBSEQUENT CAR T 681 00:26:18,960 --> 00:26:19,880 CELLS. 682 00:26:19,880 --> 00:26:21,480 NONE OF THESE STUDIES WOULD HAVE 683 00:26:21,480 --> 00:26:23,240 BEEN POSSIBLE WITHOUT HAVING THE 684 00:26:23,240 --> 00:26:24,360 EXPERTISE OVER THE PAST TEN 685 00:26:24,360 --> 00:26:26,880 YEARS TO BE ABLE TO LEARN FROM 686 00:26:26,880 --> 00:26:29,360 OUR PATIENTS AND THEIR 687 00:26:29,360 --> 00:26:30,560 EXPERIENCE. 688 00:26:30,560 --> 00:26:32,560 WE'RE THINKING ABOUT OVERCOMING 689 00:26:32,560 --> 00:26:35,080 ANTIGEN ESCAPE, BY DOING 690 00:26:35,080 --> 00:26:36,080 COMBINATORIAL TREATMENT 691 00:26:36,080 --> 00:26:36,680 STRATEGIES. 692 00:26:36,680 --> 00:26:38,760 THIS STARTED WITH CD22 WHICH WAS 693 00:26:38,760 --> 00:26:43,520 A VERY FIRST CAR T CELL THAT 694 00:26:43,520 --> 00:26:44,280 TARGETED ALTERED ANTIGEN BEYOND 695 00:26:44,280 --> 00:26:46,720 CDAND IT COULD BE JUST AS 696 00:26:46,720 --> 00:26:49,840 EFFECTIVE BUT HAD A DIFFERENT 697 00:26:49,840 --> 00:26:50,520 TOXICITY PROFILE. 698 00:26:50,520 --> 00:26:52,880 WE HAVE SERIAL EVALUATION OF 699 00:26:52,880 --> 00:26:54,600 CD19 EXPRESSION OVER TIME. 700 00:26:54,600 --> 00:26:58,000 ALSO THINKING ABOUT WHAT 701 00:26:58,000 --> 00:27:00,640 PRE-INFUSION FACTORS IMPACT THE 702 00:27:00,640 --> 00:27:02,400 RELAPSE IMMUNOPHENOTYPE FOR 703 00:27:02,400 --> 00:27:03,000 PATIENTS WHO RELAPSE FOLLOWING 704 00:27:03,000 --> 00:27:04,120 CAR T CELLS. 705 00:27:04,120 --> 00:27:05,120 OUR WORK ISN'T DONE. 706 00:27:05,120 --> 00:27:07,880 FOR THOSE PATIENTS WHO DO 707 00:27:07,880 --> 00:27:09,520 ACHIEVE A GOOD RESPONSE, WE'RE 708 00:27:09,520 --> 00:27:11,840 NOW SHIFTING GEARS INTO THINKING 709 00:27:11,840 --> 00:27:14,240 ABOUT THE LONG-TERM OUTCOMES. 710 00:27:14,240 --> 00:27:17,600 WHAT ABOUT OUTCOMES OF FOR -- 711 00:27:17,600 --> 00:27:23,440 FER FERTILITY? 712 00:27:23,440 --> 00:27:25,640 FOR PATIENTS WHO DEVELOPED 713 00:27:25,640 --> 00:27:28,160 SECONDARY MALIGNANCIES WHAT IF A 714 00:27:28,160 --> 00:27:29,560 DIAGNOSTIC APPROACH -- HOW DO 715 00:27:29,560 --> 00:27:30,800 YOU EVALUATE IN THE CONTEXT OF 716 00:27:30,800 --> 00:27:32,640 CAR T CELLS? 717 00:27:32,640 --> 00:27:33,920 WHAT ABOUT SUBACUTE TOXICITIES 718 00:27:33,920 --> 00:27:35,680 AND DELAYED EFFECT IN 719 00:27:35,680 --> 00:27:37,600 NEUROCOGNITIVE FUNCTION? 720 00:27:37,600 --> 00:27:39,440 YOU'LL HEAR ABOUT THAT LATER 721 00:27:39,440 --> 00:27:41,080 TODAY, TALKING ABOUT THAT. 722 00:27:41,080 --> 00:27:42,920 AND WHAT ABOUT THE PSYCHOSOCIAL 723 00:27:42,920 --> 00:27:43,560 CARE? 724 00:27:43,560 --> 00:27:45,880 ALL FOUR OF THESE PAPERS 725 00:27:45,880 --> 00:27:48,640 REPRESENT FIRST, THEY HAVE ALL 726 00:27:48,640 --> 00:27:50,920 COME FROM OUR GROUP. 727 00:27:50,920 --> 00:27:52,120 SO WITH THAT, I THANK YOU FOR 728 00:27:52,120 --> 00:27:53,320 THE HONOR AND PRIVILEGE OF BEING 729 00:27:53,320 --> 00:27:55,600 ABLE TO WORK WITH ALL OF YOU. 730 00:27:55,600 --> 00:27:57,040 THANK YOU FOR ALL OF THOSE WHO 731 00:27:57,040 --> 00:28:00,280 HAVE TAKEN ME UNDER THEIR WING. 732 00:28:00,280 --> 00:28:01,960 I'VE BEEN HERE SINCE 2009. 733 00:28:01,960 --> 00:28:03,880 I'VE HAD THE PRIVILEGE OF BEING 734 00:28:03,880 --> 00:28:05,160 HANDED THIS TORCH AND LOOK 735 00:28:05,160 --> 00:28:05,920 FORWARD TO CONTINUING TO WORK 736 00:28:05,920 --> 00:28:08,000 WITH ALL OF YOU AND HOPING WE 737 00:28:08,000 --> 00:28:09,960 CAN CONTINUE THIS PROGRAM AND 738 00:28:09,960 --> 00:28:10,520 MAKE YOU PROUD. 739 00:28:10,520 --> 00:28:12,360 I WANT TO THANK YOU FOR THE 740 00:28:12,360 --> 00:28:13,920 SUPPORT OUR TEAM HAS RECEIVED IN 741 00:28:13,920 --> 00:28:16,200 TAKING CARE OF OUR PATIENTS. 742 00:28:16,200 --> 00:28:17,800 FOR THE TRUST TO OUR FAMILIES, 743 00:28:17,800 --> 00:28:19,160 FOR THE TRUST YOU PUT WITH US 744 00:28:19,160 --> 00:28:21,600 FOR YOUR CHILDREN AND LOVED 745 00:28:21,600 --> 00:28:21,800 ONES. 746 00:28:21,800 --> 00:28:23,640 AND TO SAY WE MUST CONTINUE TO 747 00:28:23,640 --> 00:28:27,160 PUSH FORWARD TO MAKE THESE 748 00:28:27,160 --> 00:28:29,040 THERAPIES BETTER, SAFER, EASIER 749 00:28:29,040 --> 00:28:29,600 TO ACCESS. 750 00:28:29,600 --> 00:28:31,680 WITH THIS I'D LIKE TO INVITE 751 00:28:31,680 --> 00:28:33,320 DAVE TO COME TO THE PODIUM TO 752 00:28:33,320 --> 00:28:35,880 BEGIN HIS PART OF THE 753 00:28:35,880 --> 00:28:36,280 PRESENTATION. 754 00:28:36,280 --> 00:28:36,560 THANK YOU. 755 00:28:36,560 --> 00:28:39,400 [APPLAUSE] 756 00:28:39,400 --> 00:28:49,440 757 00:28:51,120 --> 00:28:51,880 >> THANK YOU, NIRALI. 758 00:28:51,880 --> 00:28:55,720 I'M HERE TO TALK ABOUT THE 759 00:28:55,720 --> 00:28:58,280 TREMENDOUS CHANGE, THE WORK POB 760 00:28:58,280 --> 00:29:00,280 HAD ON CELL PROCESSING. 761 00:29:00,280 --> 00:29:02,480 SO, TO SET THE STAGE, IN 2012 762 00:29:02,480 --> 00:29:04,880 WHEN WE MANUFACTURED THE FIRST 763 00:29:04,880 --> 00:29:07,120 CAR T CELL, REALLY VERY FEW 764 00:29:07,120 --> 00:29:09,280 PLACES WERE MAKING CAR T CELL. 765 00:29:09,280 --> 00:29:11,760 SURGERY BRANCH AND NCI WAS, AND 766 00:29:11,760 --> 00:29:12,120 U PENN. 767 00:29:12,120 --> 00:29:16,320 MANY OF THE THINGS DONE HERE 768 00:29:16,320 --> 00:29:17,720 WERE FIRST-IN-HUMAN, NEARLY 769 00:29:17,720 --> 00:29:19,400 FIRST-IN-HUMAN, MANUFACTURING 770 00:29:19,400 --> 00:29:21,960 EVENTS AND CLINICAL TRIALS. 771 00:29:21,960 --> 00:29:22,960 THEN THE REGULATORY ENVIRONMENT 772 00:29:22,960 --> 00:29:24,160 WAS QUITE DIFFERENT. 773 00:29:24,160 --> 00:29:25,840 WE HEARD IT WASN'T EASY TO GET 774 00:29:25,840 --> 00:29:26,800 THESE THINGS THROUGH AND 775 00:29:26,800 --> 00:29:27,160 APPROVED. 776 00:29:27,160 --> 00:29:29,880 ON THE OTHER HAND, THOUGH, IT'S 777 00:29:29,880 --> 00:29:33,040 MUCH EASIER NOW. 778 00:29:33,040 --> 00:29:34,800 WE HAD INVESTIGATOR INITIATED 779 00:29:34,800 --> 00:29:36,640 INDs AND BENCH TO BEDSIDE 780 00:29:36,640 --> 00:29:38,600 PROCESS REALLY MOVED RELATIVELY 781 00:29:38,600 --> 00:29:41,360 QUICKLY COMPARED TO NOW. 782 00:29:41,360 --> 00:29:44,520 TODAY WE HAVE MANY CAR T CELLS, 783 00:29:44,520 --> 00:29:46,480 MANY CLINICAL TRIALS INVOLVING 784 00:29:46,480 --> 00:29:48,600 CAR T CELLS. 785 00:29:48,600 --> 00:29:49,840 THE WORLD'S CHANGED, THERE ARE 786 00:29:49,840 --> 00:29:53,960 MANY COMMERCIAL CAR T CELL 787 00:29:53,960 --> 00:29:54,240 THERAPIES. 788 00:29:54,240 --> 00:29:57,240 AND FROM REGULATORY POINT OF 789 00:29:57,240 --> 00:29:59,640 VIEW, THE NCI NOW HOLDS IND 790 00:29:59,640 --> 00:30:00,360 CENTRALLY. 791 00:30:00,360 --> 00:30:03,160 SO THE WORK IN POB CHANGED 792 00:30:03,160 --> 00:30:05,200 CLINICAL MEDICINE AND REALLY 793 00:30:05,200 --> 00:30:06,960 CHANGED THE FIELD OF CELL 794 00:30:06,960 --> 00:30:07,240 THERAPIES. 795 00:30:07,240 --> 00:30:10,680 THIS IS A SLIDE THAT I LIKE TO 796 00:30:10,680 --> 00:30:10,920 SHOW. 797 00:30:10,920 --> 00:30:13,040 WE'VE BEEN DOING CELL THERAPIES 798 00:30:13,040 --> 00:30:15,760 FOR 25 YEARS AT THE NIH CLINICAL 799 00:30:15,760 --> 00:30:17,680 CENTER, REALLY 12 YEARS AGO WHEN 800 00:30:17,680 --> 00:30:19,880 IT CAME TO MANUFACTURING CELL 801 00:30:19,880 --> 00:30:20,920 THERAPIES, YES, THINGS WORKED A 802 00:30:20,920 --> 00:30:22,880 LITTLE BIT, BUT NOTHING LIKE CAR 803 00:30:22,880 --> 00:30:23,400 T CELLS. 804 00:30:23,400 --> 00:30:26,040 SO IT WAS KIND OF A SLEEPY FIELD 805 00:30:26,040 --> 00:30:27,360 AND WE DIDN'T GET MUCH 806 00:30:27,360 --> 00:30:27,680 ATTENTION. 807 00:30:27,680 --> 00:30:30,360 WE DID HAVE PEOPLE THOUGH THAT 808 00:30:30,360 --> 00:30:31,560 WERE PERSISTENT AND MOVED 809 00:30:31,560 --> 00:30:31,880 FORWARD. 810 00:30:31,880 --> 00:30:35,160 WE HAD FUNDING BUT IT DIDN'T 811 00:30:35,160 --> 00:30:35,600 CHANGE. 812 00:30:35,600 --> 00:30:37,360 PEOPLE FROM A REGULATORY AND 813 00:30:37,360 --> 00:30:39,200 PERFORMANCE POINT OF VIEW, 814 00:30:39,200 --> 00:30:40,760 PEOPLE LEFT US ALONE. 815 00:30:40,760 --> 00:30:43,040 TEN YEARS AGO, THE SUCCESS OF 816 00:30:43,040 --> 00:30:46,840 CAR T CELLS, PEOPLE BECAME 817 00:30:46,840 --> 00:30:48,080 VERY -- CLINICIANS BECAME 818 00:30:48,080 --> 00:30:48,920 INTERESTED IN MAKING CAR T 819 00:30:48,920 --> 00:30:49,160 CELLS. 820 00:30:49,160 --> 00:30:51,840 WE GOT A LITTLE MORE FUNDING 821 00:30:51,840 --> 00:30:54,800 FROM THE CLINICAL CENTER. 822 00:30:54,800 --> 00:30:56,840 THEIR PERFORMANCE EXPECTATIONS 823 00:30:56,840 --> 00:30:57,520 AND REGULATORY EXPECTATIONS 824 00:30:57,520 --> 00:30:59,120 CHANGED A LITTLE BIT BUT REALLY 825 00:30:59,120 --> 00:31:02,320 WE DIDN'T GET A LOT OF OTHER 826 00:31:02,320 --> 00:31:03,400 ATTENTION FROM PEOPLE. 827 00:31:03,400 --> 00:31:08,800 FIVE OR TEN YEARS AGO WHEN CAR T 828 00:31:08,800 --> 00:31:10,520 CELLS PROVED SO SUCCESSFUL AND 829 00:31:10,520 --> 00:31:11,600 EVERYTHING WORKED, NOW EVERYBODY 830 00:31:11,600 --> 00:31:14,600 CARES, WE HAVE A LOT MORE 831 00:31:14,600 --> 00:31:15,640 FUNDING FOR CELL THERAPY, 832 00:31:15,640 --> 00:31:17,760 INDUSTRIES INVOLVED, AND REALLY 833 00:31:17,760 --> 00:31:19,280 THE FDA, THEIR INVOLVEMENT IN 834 00:31:19,280 --> 00:31:20,920 THE FIELD HAS GROWN 835 00:31:20,920 --> 00:31:22,240 SIGNIFICANTLY AND WE'RE EXPECTED 836 00:31:22,240 --> 00:31:27,800 TO PERFORM LIKE A PHARMA 837 00:31:27,800 --> 00:31:28,040 COMPANY. 838 00:31:28,040 --> 00:31:29,760 SO, FOR THE FIRST 25 YEARS OF 839 00:31:29,760 --> 00:31:31,520 THE CELL THERAPY GROUP, WE WERE 840 00:31:31,520 --> 00:31:34,160 ONE PART OF THE DEPARTMENT OF 841 00:31:34,160 --> 00:31:36,200 TRANSFUSION MEDICINE, THEY HAVE 842 00:31:36,200 --> 00:31:37,760 THE TRANSFUSION SERVICE, BLOOD 843 00:31:37,760 --> 00:31:38,600 COLLECTION GROUP, INFECTIOUS 844 00:31:38,600 --> 00:31:39,400 DISEASE SECTION. 845 00:31:39,400 --> 00:31:42,600 AND WE'RE THE CELL PROCESSING 846 00:31:42,600 --> 00:31:43,360 SECTION. 847 00:31:43,360 --> 00:31:45,280 BUT BASED ON TREMENDOUS GROWTH 848 00:31:45,280 --> 00:31:48,160 OF CAR T CELLS AND OTHER CANCER 849 00:31:48,160 --> 00:31:48,720 IMMUNOTHERAPIES, ABOUT THREE 850 00:31:48,720 --> 00:31:54,720 YEARS AGO THE CENTER OF CELLULAR 851 00:31:54,720 --> 00:31:56,360 ENGINEERING WAS FORMED. 852 00:31:56,360 --> 00:32:02,080 NOW WE HAVE FOUR SECTIONS OF 853 00:32:02,080 --> 00:32:06,680 PRODUCT DEVELOPMENT, 854 00:32:06,680 --> 00:32:07,440 MANUFACTURING SECTION, ASSAY 855 00:32:07,440 --> 00:32:08,960 SECTION, SERVICE COORDINATION, 856 00:32:08,960 --> 00:32:10,400 WE HAVE A LARGE QUALITY GROUP. 857 00:32:10,400 --> 00:32:12,720 I DON'T WANT TO GO IN GREAT 858 00:32:12,720 --> 00:32:15,880 DETAIL BUT WE HAVE MADE A LOT OF 859 00:32:15,880 --> 00:32:20,400 DIFFERENT KIND OF CAR T CELLS, 860 00:32:20,400 --> 00:32:22,440 CD19, CD22, AND BY SPECIFIC 861 00:32:22,440 --> 00:32:29,880 WE'VE ALSO MADE CAR T CELLS FOR 862 00:32:29,880 --> 00:32:31,520 DR. COKENDORF TO TREAT PATIENTS. 863 00:32:31,520 --> 00:32:34,600 AND RECENTLY WE TREATED THE 864 00:32:34,600 --> 00:32:36,360 FIRST PATIENT WITH CD22 CAR T 865 00:32:36,360 --> 00:32:38,120 CELLS WITH HAIRY CELL LEUKEMIA, 866 00:32:38,120 --> 00:32:41,720 WE'VE MADE CAR T CELLS FOR SOME 867 00:32:41,720 --> 00:32:43,040 SOLID TUMORS. 868 00:32:43,040 --> 00:32:44,560 SO, ONE OF THE BIG CHANGES IN 869 00:32:44,560 --> 00:32:47,240 THE FIELD IS THAT WITH THE 870 00:32:47,240 --> 00:32:50,600 SUCCESS OF CAR T CELLS, A NUMBER 871 00:32:50,600 --> 00:32:52,240 OF MANUFACTURERS HAVE GOT 872 00:32:52,240 --> 00:32:54,080 INTERESTED IN THE FIELD. 873 00:32:54,080 --> 00:32:56,480 SO NOW THE EQUIPMENT AVAILABLE 874 00:32:56,480 --> 00:32:58,760 FOR US TO MAKE CAR T CELLS AND 875 00:32:58,760 --> 00:33:01,280 AGENTS AVAILABLE TO MAKE THEM 876 00:33:01,280 --> 00:33:04,800 ARE MUCH IMPROVED. 877 00:33:04,800 --> 00:33:05,680 THERE'S AUTOMATED BIOREACTORS 878 00:33:05,680 --> 00:33:07,040 THAT ARE PURPOSE BUILD OF BUILT 879 00:33:07,040 --> 00:33:08,520 TO MAKE CAR T CELLS. 880 00:33:08,520 --> 00:33:11,480 WE HAVE CELL WASHERS AND CELL 881 00:33:11,480 --> 00:33:13,240 SEPARATORS THAT ARE BUILT TO 882 00:33:13,240 --> 00:33:14,760 WASH AND SEPARATE CELLS FOR 883 00:33:14,760 --> 00:33:15,640 MAKING CAR T CELLS. 884 00:33:15,640 --> 00:33:23,080 THERE'S A NUMBER OF VERY GOOD 885 00:33:23,080 --> 00:33:26,160 GNP REAGENTS TO BUY OFF THE 886 00:33:26,160 --> 00:33:27,280 SHELF. 887 00:33:27,280 --> 00:33:30,440 WHY IS THIS IMPORTANT? 888 00:33:30,440 --> 00:33:40,600 IT'S MADED -- MADE IT EASIER 889 00:33:40,600 --> 00:33:42,040 AND MANY ACADEMIC CENTERS ARE 890 00:33:42,040 --> 00:33:44,200 MAKING CAR T CELLS. 891 00:33:44,200 --> 00:33:48,920 THE OTHER CHANGE WE'VE SEEN IS 892 00:33:48,920 --> 00:33:51,320 INVOLVING ISSUE WHERE WE COLLECT 893 00:33:51,320 --> 00:33:52,720 CELLS, AUTOLOGOUS CELLS FROM 894 00:33:52,720 --> 00:33:54,600 PATIENTS NEEDING CAR T CELL 895 00:33:54,600 --> 00:33:56,240 THERAPY OR OTHER CANCER 896 00:33:56,240 --> 00:33:57,880 IMMUNOTHERAPIES IN THE 897 00:33:57,880 --> 00:33:58,560 DEPARTMENT OF TRANSFUSION 898 00:33:58,560 --> 00:33:58,800 MEDICINE. 899 00:33:58,800 --> 00:34:01,480 WE SEND THEM OFF TO COMPANIES 900 00:34:01,480 --> 00:34:02,920 FOR FURTHER MANUFACTURING. 901 00:34:02,920 --> 00:34:04,560 THOSE CELLS ARE COLLECTED HERE, 902 00:34:04,560 --> 00:34:07,200 THEY COME TO OUR LAB. 903 00:34:07,200 --> 00:34:08,640 WE LABEL THEM AND DOCUMENT 904 00:34:08,640 --> 00:34:10,800 THINGS, PACK THEM UP AND SEND 905 00:34:10,800 --> 00:34:13,160 THEM OFF TO A COMPANY, THE 906 00:34:13,160 --> 00:34:16,400 COMPANIES MAKE A CAR T CELL OR 907 00:34:16,400 --> 00:34:17,800 OTHER CANCER IMMUNOTHERAPY. 908 00:34:17,800 --> 00:34:19,960 WHEN THE MANUFACTURING IS DONE, 909 00:34:19,960 --> 00:34:21,320 THE PRODUCTS ARE FROZEN. 910 00:34:21,320 --> 00:34:22,800 WHEN LOT RELEASE TESTING IS DONE 911 00:34:22,800 --> 00:34:24,040 THEY SEND THEM BACK TO US, WHERE 912 00:34:24,040 --> 00:34:26,440 THEY ARE STORED UNTIL THE 913 00:34:26,440 --> 00:34:27,760 PATIENT NEEDS TO BE TREATED. 914 00:34:27,760 --> 00:34:32,000 THIS IS A VERY IMPORTANT PART OF 915 00:34:32,000 --> 00:34:33,200 TREATING PATIENTS WITH LEUKEMIAS 916 00:34:33,200 --> 00:34:34,240 AND LYMPHOMAS, BUT IT'S ALSO 917 00:34:34,240 --> 00:34:36,560 BECOME A VERY BIG PART OF OUR 918 00:34:36,560 --> 00:34:39,640 BUSINESS AND SOMETHING THAT'S 919 00:34:39,640 --> 00:34:41,240 TOTALLY NEW SINCE 2012. 920 00:34:41,240 --> 00:34:43,280 SO, WHERE ARE WE GOING FROM NOW 921 00:34:43,280 --> 00:34:44,840 TO MEET NEEDS? 922 00:34:44,840 --> 00:34:48,560 IT'S CLEAR TO US THAT IT'S VERY 923 00:34:48,560 --> 00:34:51,720 IMPORTANT EVERY TIME WE TRY AND 924 00:34:51,720 --> 00:34:53,920 MANUFACTURE CAR T CELL, WE WERE 925 00:34:53,920 --> 00:34:55,840 SUCCESSFUL AND WE MANUFACTURE A 926 00:34:55,840 --> 00:34:57,880 VERY HIGH QUALITY PRODUCT. 927 00:34:57,880 --> 00:35:00,840 WE CONSTANTLY WORK ON OPTIMIZING 928 00:35:00,840 --> 00:35:02,800 THE MANUFACTURING PROCESS. 929 00:35:02,800 --> 00:35:05,560 WE'RE ALSO LOOKING AT THE BEST, 930 00:35:05,560 --> 00:35:08,440 HOW TO OPTIMIZE PATIENT CELLS, 931 00:35:08,440 --> 00:35:09,160 TO BEGIN MANUFACTURING. 932 00:35:09,160 --> 00:35:12,520 AGAIN, SO WE GET THE BEST 933 00:35:12,520 --> 00:35:12,880 PRODUCT. 934 00:35:12,880 --> 00:35:15,280 WE'RE ALSO WORKING WITH, AGAIN, 935 00:35:15,280 --> 00:35:18,680 POB AND OTHERS TO MAKE CELLULAR 936 00:35:18,680 --> 00:35:20,720 IMMUNOTHERAPY SUCCESSFUL FOR 937 00:35:20,720 --> 00:35:22,600 PATIENTS WITH CANCER. 938 00:35:22,600 --> 00:35:24,960 IN CLOSING, I WANT TO MENTION 939 00:35:24,960 --> 00:35:26,120 FROM MY POINT OF VIEW THIS HAS 940 00:35:26,120 --> 00:35:28,520 BEEN ONE OF THE BEST 941 00:35:28,520 --> 00:35:29,920 PROFESSIONAL EXPERIENCES OF MY 942 00:35:29,920 --> 00:35:31,440 LIFE, IT'S BEEN INCREDIBLE TO 943 00:35:31,440 --> 00:35:35,920 WATCH THE DEVELOPMENT OF THIS 944 00:35:35,920 --> 00:35:37,960 ENTIRELY NEW CANCER THERAPY. 945 00:35:37,960 --> 00:35:41,240 I WAS ALLOWED BY POB, ME AND ALL 946 00:35:41,240 --> 00:35:44,040 THE OTHERS IN THE CCE, WERE 947 00:35:44,040 --> 00:35:46,480 BROUGHT INTO THIS. 948 00:35:46,480 --> 00:35:48,440 AND WE WERE ALLOWED TO HELP 949 00:35:48,440 --> 00:35:49,880 ADVANCE THIS FIELD, IT'S BEEN 950 00:35:49,880 --> 00:35:51,080 TERRIFIC TO EXPERIENCE THE 951 00:35:51,080 --> 00:35:52,080 FUNDAMENTAL CHANGE IN CLINICAL 952 00:35:52,080 --> 00:35:55,520 MEDICINE AND THE FIELD OF CELL 953 00:35:55,520 --> 00:35:55,760 THERAPY. 954 00:35:55,760 --> 00:35:57,480 THANK YOU, POB. 955 00:35:57,480 --> 00:36:04,640 [APPLAUSE] 956 00:36:04,640 --> 00:36:06,360 >>IT IS MY GREAT PRIVILEGE AND 957 00:36:06,360 --> 00:36:08,240 HONOR TO WELCOME DR. ROSENBERG 958 00:36:08,240 --> 00:36:12,960 TO GIVE A KEYNOTE AND TALK ABOUT 959 00:36:12,960 --> 00:36:14,920 THE HISTORY OF CD19 CAR T CELLS. 960 00:36:14,920 --> 00:36:16,360 I THINK WHAT YOU SAW IN THE 961 00:36:16,360 --> 00:36:17,880 FIRST PART IS HOW FAR WE'VE COME 962 00:36:17,880 --> 00:36:19,880 BUT HE WILL TELL YOU MORE ABOUT 963 00:36:19,880 --> 00:36:21,520 HOW IT ALL STARTED. 964 00:36:21,520 --> 00:36:24,200 SO THANK YOU. 965 00:36:24,200 --> 00:36:30,240 966 00:36:30,240 --> 00:36:36,240 967 00:36:36,240 --> 00:36:37,800 >> I'LL TRY IN THE NEXT TEN 968 00:36:37,800 --> 00:36:39,320 MINUTES TO TALK ABOUT THE LAST 969 00:36:39,320 --> 00:36:43,720 THREE OR FOUR YEARS OF OUR WORK 970 00:36:43,720 --> 00:36:47,360 TRYING TO DEVELOP THESE 971 00:36:47,360 --> 00:36:48,760 TREATMENTS. 972 00:36:48,760 --> 00:36:51,600 IN MY VIEW IT STARTED BACK IN 973 00:36:51,600 --> 00:36:52,920 1988 WHEN WE PUBLISHED A PAPER 974 00:36:52,920 --> 00:36:56,840 IN THE NEW ENGLAND JOURNAL, THE 975 00:36:56,840 --> 00:36:59,040 FIRST PAPER SHOWING TUMOR 976 00:36:59,040 --> 00:36:59,680 INFILTRATING LYMPHOCYTES, THAT 977 00:36:59,680 --> 00:37:02,200 WE COULD ISOLATE AND GROW OUT OF 978 00:37:02,200 --> 00:37:04,160 A GROWING TUMOR, GROWN TO LARGE 979 00:37:04,160 --> 00:37:09,320 AMOUNT ALSO IN VITRO IN 980 00:37:09,320 --> 00:37:10,960 INTERLEUKIN-2 AND REINFUSED TO 981 00:37:10,960 --> 00:37:11,840 MEDIATE OBJECTIVE REGRESSION, 982 00:37:11,840 --> 00:37:14,360 THE FIRST REPORT. 983 00:37:14,360 --> 00:37:16,120 WE CANNOTTED THESE STUDIES AND 984 00:37:16,120 --> 00:37:17,920 HAVE OVER A 50% OBJECTIVE 985 00:37:17,920 --> 00:37:21,360 RESPONSE RATE NOW WITH A 986 00:37:21,360 --> 00:37:22,680 QUARTER OF THOSE PATIENTS 987 00:37:22,680 --> 00:37:24,320 COMPLETE DURABLE RESPONSES, THE 988 00:37:24,320 --> 00:37:26,280 FIRST DEMONSTRATION YOU COULD 989 00:37:26,280 --> 00:37:28,600 USE LYMPHOCYTES AS A LIVING DRUG 990 00:37:28,600 --> 00:37:31,640 TO MEDIATE CANCER AGGRESSION. 991 00:37:31,640 --> 00:37:32,200 WE'VE UTILIZED NATURALLY 992 00:37:32,200 --> 00:37:34,600 OCCURRING CELLS BUT ALMOST 993 00:37:34,600 --> 00:37:35,640 IMMEDIATELY WE BEGAN STUDIES TO 994 00:37:35,640 --> 00:37:37,760 SEE IF WE COULD GENETICALLY 995 00:37:37,760 --> 00:37:40,680 MODIFY THESE CELLS TO IMPROVE 996 00:37:40,680 --> 00:37:42,480 THEIR ANTI-TUMOR ACTIVITY. 997 00:37:42,480 --> 00:37:44,760 AND THAT INVOLVED GENETIC 998 00:37:44,760 --> 00:37:45,720 MODIFICATION OF CELLS, 999 00:37:45,720 --> 00:37:47,520 ADMINISTERED TO PATIENTS WHICH 1000 00:37:47,520 --> 00:37:49,280 HADN'T BEEN DONE, A 1001 00:37:49,280 --> 00:37:52,960 CONTROVERSIAL ISSUE, BUT I BEGAN 1002 00:37:52,960 --> 00:38:03,520 COLLABORATIONS WITH THOSE TO MY 1003 00:38:03,760 --> 00:38:06,080 RIGHT TO GENETICALLY MODIFY. 1004 00:38:06,080 --> 00:38:07,960 WE SELECTED A BACTERIAL GENE, 1005 00:38:07,960 --> 00:38:11,120 THAT WOULD ENABLE US TO TRAFFIC 1006 00:38:11,120 --> 00:38:14,520 THESE CELLS FOLLOWING THEIR IN 1007 00:38:14,520 --> 00:38:19,240 VIVO ADMINISTRATION AND 1008 00:38:19,240 --> 00:38:21,760 DISTINGUISH THEM FROM ENDOGENOUS 1009 00:38:21,760 --> 00:38:22,080 LYMPHOCYTES. 1010 00:38:22,080 --> 00:38:23,960 WE WENT THROUGH 16 REVIEW 1011 00:38:23,960 --> 00:38:28,440 GROUPS, AND I TOOK THIS NOTE 1012 00:38:28,440 --> 00:38:30,760 FROM MY NOTEBOOK, WE WENT 1013 00:38:30,760 --> 00:38:34,800 THROUGH THE IRB, BIOSAFETY 1014 00:38:34,800 --> 00:38:35,760 COMMITTEES, NIH ESTABLISHED 1015 00:38:35,760 --> 00:38:39,160 RECOMBINANT COMMITTEE TO LOOK AT 1016 00:38:39,160 --> 00:38:43,120 THESE MANIPULATIONS WITH 1017 00:38:43,120 --> 00:38:46,400 RECOMBINANT CELLS, AND THE RAC 1018 00:38:46,400 --> 00:38:49,480 VOTED TO ALLOW US TO PROCEED 1019 00:38:49,480 --> 00:38:54,800 WITH THE 16-5 NOTE, BUT THE 1020 00:38:54,800 --> 00:38:55,800 DIRECTOR, JIM WYNGAARDEN, SAID 1021 00:38:55,800 --> 00:38:57,120 THAT WAS NOT GOOD ENOUGH. 1022 00:38:57,120 --> 00:39:00,840 IF WE WOULD BE PUTTING FOREIGN 1023 00:39:00,840 --> 00:39:02,920 GENES INTO PEOPLE FOR THE FIRST 1024 00:39:02,920 --> 00:39:06,400 TIME WE NEEDED A UNANIMOUS VOTE, 1025 00:39:06,400 --> 00:39:11,360 WE HAD GO BACK BASED ON WHAT WAS 1026 00:39:11,360 --> 00:39:14,280 SUGGESTED UNTIL FINALLY IN 1988 1027 00:39:14,280 --> 00:39:15,600 THE RAC VOTED 13-0, ONE 1028 00:39:15,600 --> 00:39:17,360 ABSTENTION, TO ENABLE US TO 1029 00:39:17,360 --> 00:39:17,680 PROCEED. 1030 00:39:17,680 --> 00:39:20,560 WE WENT BACK THROUGH THE REVIEW 1031 00:39:20,560 --> 00:39:26,720 GROUPS AND ON MAY 22 TREATED OUR 1032 00:39:26,720 --> 00:39:29,080 FIRST PATIENT, IN 1989. 1033 00:39:29,080 --> 00:39:30,960 DELAYED BECAUSE JEREMY, A 1034 00:39:30,960 --> 00:39:32,160 BIOTECHNOLOGY ACTIVIST, FILED A 1035 00:39:32,160 --> 00:39:33,360 LAWSUIT AGAINST THE NIH TO 1036 00:39:33,360 --> 00:39:35,320 PREVENT US FROM DOING THIS. 1037 00:39:35,320 --> 00:39:37,960 THEY DIDN'T FEEL ANYONE SHOULD 1038 00:39:37,960 --> 00:39:39,160 BE TAMPERING WITH GOD'S DNA IN 1039 00:39:39,160 --> 00:39:41,880 PATIENTS, BUT THAT WAS FINALLY 1040 00:39:41,880 --> 00:39:42,160 RESOLVED. 1041 00:39:42,160 --> 00:39:46,720 WE WERE ABLE TO PROCEED. 1042 00:39:46,720 --> 00:39:49,040 1990 PUBLISHED THIS PAPER IN THE 1043 00:39:49,040 --> 00:39:50,440 NEW ENGLAND JOURNAL SHOWING THIS 1044 00:39:50,440 --> 00:39:53,080 COULD BE SAFELILY DONE 1045 00:39:53,080 --> 00:39:54,440 RETROVIRALLY TRANSDUCING CELLS, 1046 00:39:54,440 --> 00:39:57,960 SAFE, MONITORING CELLS TO LOOK 1047 00:39:57,960 --> 00:39:59,440 AT SURVIVAL IN PATIENTS. 1048 00:39:59,440 --> 00:40:01,400 THAT LED US TO A LOT OF 1049 00:40:01,400 --> 00:40:03,600 LABORATORY WORK UNTIL FINALLY 1050 00:40:03,600 --> 00:40:05,720 THIS PAPER IN 2006, THE FIRST 1051 00:40:05,720 --> 00:40:09,080 TIME WE COULD ACTUALLY INTRODUCE 1052 00:40:09,080 --> 00:40:11,720 GENETICALLY MODIFIED CELLS THAT 1053 00:40:11,720 --> 00:40:13,480 HAD BEEN RETROVIRALLY 1054 00:40:13,480 --> 00:40:22,480 TRANSDEUCED WITH T T-CELL 1055 00:40:22,480 --> 00:40:25,440 RECEPTORS THAT RECOGNIZED IN 1056 00:40:25,440 --> 00:40:27,720 MELANOMA, SAW TWO RESPONSES IN 1057 00:40:27,720 --> 00:40:29,080 THOSE PATIENTS, BUT AT LEAST IT 1058 00:40:29,080 --> 00:40:33,880 DID SHOW WE COULD TAKE A NORMAL 1059 00:40:33,880 --> 00:40:35,520 LYMPHOCYTE, INSERT T-CELL 1060 00:40:35,520 --> 00:40:38,120 RECEPTOR, SHOW TUMOR REGRESSION. 1061 00:40:38,120 --> 00:40:40,200 WE THEN PUBLISHED A COUPLE YEARS 1062 00:40:40,200 --> 00:40:46,800 LATER, USE OF A VERY HIGHLY AVID 1063 00:40:46,800 --> 00:40:48,120 T-CELL RECEPTOR RECOGNIZING IN 1064 00:40:48,120 --> 00:40:50,080 SIX OUT OF TWENTY PATIENTS, 30% 1065 00:40:50,080 --> 00:40:52,160 OF PATIENTS THEN HAD OBJECTIVE 1066 00:40:52,160 --> 00:40:54,680 RESPONSES WITH THEIR OWN NORMAL 1067 00:40:54,680 --> 00:40:58,480 LYMPHOCYTES TRANSDUCED WITH THIS 1068 00:40:58,480 --> 00:40:59,720 RECEPTOR RECOGNIZING MART-1, AND 1069 00:40:59,720 --> 00:41:01,680 A COUPLE YEARS LATER WHEN WE 1070 00:41:01,680 --> 00:41:04,880 BEGAN OUR INTERACTIONS WITH THE 1071 00:41:04,880 --> 00:41:06,360 PEDIATRIC ONCOLOGY BRANCH IN 1072 00:41:06,360 --> 00:41:09,440 2011, WE LOOKED AT T CELLS THAT 1073 00:41:09,440 --> 00:41:10,440 WERE TRANSDUCED WITH T-CELL 1074 00:41:10,440 --> 00:41:15,560 RECEPTORS THAT RECOGNIZED A CAN 1075 00:41:15,560 --> 00:41:17,760 SORRY GERMLINE ANTIGEN NY-ESO-1, 1076 00:41:17,760 --> 00:41:28,320 AND IN THESE PATIENTS 4 OUT OF 6 1077 00:41:28,800 --> 00:41:31,800 SYNOVIAL SARCOMA. 1078 00:41:31,800 --> 00:41:33,320 THE CD19 STORY BEGAN, CD19 AS 1079 00:41:33,320 --> 00:41:38,200 YOU'VE HEARD IS A MOLECULE 1080 00:41:38,200 --> 00:41:41,640 EXPRESSED ON NORMAL B 1081 00:41:41,640 --> 00:41:44,560 LYMPHOCYTES, IN 2007 GOING ON 1082 00:41:44,560 --> 00:41:46,560 2008, A FELLOW IN HEMATOLOGY 1083 00:41:46,560 --> 00:41:47,560 ONCOLOGY TRAINING PROGRAM JOINED 1084 00:41:47,560 --> 00:41:48,840 MY LAB AND BEGAN TO EXPLORE 1085 00:41:48,840 --> 00:41:52,120 WHETHER OR NOT WE COULD TARGET 1086 00:41:52,120 --> 00:41:53,880 CD19 IN PATIENTS. 1087 00:41:53,880 --> 00:42:01,040 AND HE DID ELEGANT STUDIES IN 1088 00:42:01,040 --> 00:42:02,960 ANIMAL MODELS SHOWING LYMPHOMAS 1089 00:42:02,960 --> 00:42:04,480 COULD BE ELIMINATED IN 2009 1090 00:42:04,480 --> 00:42:13,320 TREATED OUR FIRST PATIENT WITH A 1091 00:42:13,320 --> 00:42:14,160 HUMAN RECEPTOR, PUBLISHED THAT 1092 00:42:14,160 --> 00:42:17,240 IN 2010, THAT BEGAN OUR STUDIES 1093 00:42:17,240 --> 00:42:20,200 WITH CD19 ABOUT A YEAR LATER, 1094 00:42:20,200 --> 00:42:21,160 CARL JUNE REPORTED EFFECTIVE 1095 00:42:21,160 --> 00:42:24,560 TREATMENT OF USE OF CD19 CAR T 1096 00:42:24,560 --> 00:42:27,000 CELLS COULD DO THIS AS WELL. 1097 00:42:27,000 --> 00:42:29,240 THIS WAS THE FIRST PATIENT 1098 00:42:29,240 --> 00:42:31,000 TREATED, A 48-YEAR-OLD 1099 00:42:31,000 --> 00:42:32,560 CONSTRUCTION WORKER FROM 1100 00:42:32,560 --> 00:42:34,880 FLORIDA, YOU CAN SEE ON THE LEFT 1101 00:42:34,880 --> 00:42:38,040 THE LARGE TUMOR MASSES THAT WERE 1102 00:42:38,040 --> 00:42:47,120 PRESENT IN THIS PATIENT . 1103 00:42:47,120 --> 00:42:48,760 HE UNDERWENT A COMPLETE 1104 00:42:48,760 --> 00:42:52,480 REGRESSION OF ALL OF HIS 1105 00:42:52,480 --> 00:42:53,560 LYMPHOMA. 1106 00:42:53,560 --> 00:42:55,240 UNDERGONE FOUR PRIOR COMBINATION 1107 00:42:55,240 --> 00:42:56,880 CHEMOTHERAPY REGIMENS, HAD TUMOR 1108 00:42:56,880 --> 00:42:58,600 REPLACING HIS MARROW THAT 1109 00:42:58,600 --> 00:43:00,400 DISAPPEARED AS WELL. 1110 00:43:00,400 --> 00:43:04,600 AND HE'S BEEN IN ONGOING 1111 00:43:04,600 --> 00:43:08,240 COMPLETE RESPONSE NOW SINCE 1112 00:43:08,240 --> 00:43:10,840 2009, 13 YEARS LATER. 1113 00:43:10,840 --> 00:43:13,520 WHAT WE THEN BEGAN TREATING 1114 00:43:13,520 --> 00:43:15,280 PATIENTS, I BRING THIS UP TO THE 1115 00:43:15,280 --> 00:43:17,800 TIME WE BEGAN OUR INTERACTIONS, 1116 00:43:17,800 --> 00:43:20,880 WE TREATED EIGHT PATIENTS IN THE 1117 00:43:20,880 --> 00:43:23,360 SURGERY BRANCH BETWEEN JUNE OF 1118 00:43:23,360 --> 00:43:25,560 2009 AND JANUARY OF 2011, FOUR 1119 00:43:25,560 --> 00:43:28,320 PATIENTS WITH METASTATIC -- 1120 00:43:28,320 --> 00:43:32,160 WIDELY SPREAD LYMPHOMAS, WE HAD 1121 00:43:32,160 --> 00:43:33,560 FOUR PATIENTS WHO HAD COMPLETE 1122 00:43:33,560 --> 00:43:35,840 RESPONSES OUT OF THESE EIGHT, 1123 00:43:35,840 --> 00:43:37,800 INTERESTINGLY ALL FOUR OF THOSE 1124 00:43:37,800 --> 00:43:38,440 PATIENTS REMAIN COMPLETELY 1125 00:43:38,440 --> 00:43:41,240 DISEASE FREE TO THE PRESENT 1126 00:43:41,240 --> 00:43:42,240 TIME. 1127 00:43:42,240 --> 00:43:43,200 TWO PARTIAL RESPONSES, ONE 1128 00:43:43,200 --> 00:43:45,280 NON-RESPONDER, ONE PATIENT HAD A 1129 00:43:45,280 --> 00:43:51,480 TREATMENT RELATED MORTALITY. 1130 00:43:51,480 --> 00:43:56,520 SEPT 15, I WAS CONTACTED TO SEE 1131 00:43:56,520 --> 00:43:58,960 WE COULD ATTAIN ANTI-CD19 1132 00:43:58,960 --> 00:44:00,360 SUPERNATANT, TRANSFERRED FIVE 1133 00:44:00,360 --> 00:44:02,000 CASSETTES TO THE PEDIATRIC 1134 00:44:02,000 --> 00:44:06,920 ONCOLOGY BRANCH, AND THEN IN 1135 00:44:06,920 --> 00:44:09,800 MARCH OF 2012, 18 CASSETTES OF 1136 00:44:09,800 --> 00:44:13,160 THE GMP MATERIAL WE DEVELOPED 1137 00:44:13,160 --> 00:44:15,880 FORECLINICAL TRIAL, JULY 13, 1138 00:44:15,880 --> 00:44:19,320 2012, FIRST PEDIATRIC ONCOLOGY 1139 00:44:19,320 --> 00:44:21,160 BRANCH PATIENT WAS TREATED. 1140 00:44:21,160 --> 00:44:22,680 JUST AS -- I WON'T GO INTO THAT, 1141 00:44:22,680 --> 00:44:24,320 YOU HEARD FROM THE GROUP THAT 1142 00:44:24,320 --> 00:44:28,360 ACTUALLY DID THE WORK IN 1143 00:44:28,360 --> 00:44:29,680 PEDIATRICS ALREADY, BUT JUST AS 1144 00:44:29,680 --> 00:44:33,320 A POST SCRIPT TO THIS EFFORT, 1145 00:44:33,320 --> 00:44:34,800 INTERESTINGLY IN 2011 I WAS 1146 00:44:34,800 --> 00:44:38,200 CONTACTED BY A FORMER FELLOW, 1147 00:44:38,200 --> 00:44:40,520 HAD BEEN A SURGERY BRANCH 20 1148 00:44:40,520 --> 00:44:42,280 YEARS EARLIER, A UROLOGIST AT 1149 00:44:42,280 --> 00:44:45,640 UCLA, WE HAD BEEN IN TOUCH, HE 1150 00:44:45,640 --> 00:44:48,160 CAME TO SEE WHAT WE WERE DOING 1151 00:44:48,160 --> 00:44:53,880 AND WONDER WHETHER HE COULD 1152 00:44:53,880 --> 00:44:54,960 COMMERCIALLY DEVELOP THIS. 1153 00:44:54,960 --> 00:44:57,480 OTHERS REVIEWED THE DATA, IF WE 1154 00:44:57,480 --> 00:44:58,640 HAD THIS DISEASE WE WOULD BE 1155 00:44:58,640 --> 00:44:59,920 DELIGHTED TO COME TO YOU FOR 1156 00:44:59,920 --> 00:45:01,440 TREATMENT BUT DON'T SEE HOW WE 1157 00:45:01,440 --> 00:45:04,280 CAN COMMERCIALIZE AND MAKE ANY 1158 00:45:04,280 --> 00:45:06,680 MONEY WITH THIS. 1159 00:45:06,680 --> 00:45:09,520 BUT ARI STARTED KITE PHARMA, IN 1160 00:45:09,520 --> 00:45:11,160 2011, WE SIGNED A COOPERATIVE 1161 00:45:11,160 --> 00:45:12,480 RESEARCH AND DEVELOPMENT 1162 00:45:12,480 --> 00:45:14,320 AGREEMENT TO TRANSFER TECHNOLOGY 1163 00:45:14,320 --> 00:45:18,480 TO KITE PHARMA, YOU CAN SEE IN A 1164 00:45:18,480 --> 00:45:19,840 MULTI-INSTITUTIONAL STUDY HE 1165 00:45:19,840 --> 00:45:21,040 ALMOST EXACTLY REPRODUCED OUR 1166 00:45:21,040 --> 00:45:22,120 RESULTS IN THE SURGERY BRANCH UP 1167 00:45:22,120 --> 00:45:24,520 TO THAT TIME WITH OBJECTIVE 1168 00:45:24,520 --> 00:45:27,680 RESPONSE RATES IN THE 70 TO 80% 1169 00:45:27,680 --> 00:45:30,880 RANGE, COMPLETE REGRESSIONS IN 1170 00:45:30,880 --> 00:45:33,800 ABOUT THE 50% RANGE. 1171 00:45:33,800 --> 00:45:35,240 IN 2017, KITE RECEIVED FDA 1172 00:45:35,240 --> 00:45:38,760 APPROVAL AND WAS SOLD TO GILEAD 1173 00:45:38,760 --> 00:45:41,280 SCIENCES FOR $11.9 BILLION, SO 1174 00:45:41,280 --> 00:45:44,040 KITE PHARMA WENT FROM ZERO TO 1175 00:45:44,040 --> 00:45:45,320 $11.9 BILLION IN FIVE YEARS. 1176 00:45:45,320 --> 00:45:48,360 I SEE THIS AS A VERY PROUD 1177 00:45:48,360 --> 00:45:52,000 EXAMPLE OF HOW BASIC SCIENCE AND 1178 00:45:52,000 --> 00:45:53,280 NEW TREATMENTS THAT ARE 1179 00:45:53,280 --> 00:45:54,680 DEVELOPED IN ACADEMIC SETTINGS 1180 00:45:54,680 --> 00:45:56,040 AND ESPECIALLY THIS ONE HERE AT 1181 00:45:56,040 --> 00:45:59,000 THE NIH COULD BE BROUGHT TO MANY 1182 00:45:59,000 --> 00:46:00,720 PEOPLE AROUND THE WORLD, AND 1183 00:46:00,720 --> 00:46:03,360 PEOPLE NOW IN THE UNITED STATES, 1184 00:46:03,360 --> 00:46:07,160 EUROPE, BEGINNING IN ASIA ARE 1185 00:46:07,160 --> 00:46:09,480 RECEIVING THIS CD19 FOR THE 1186 00:46:09,480 --> 00:46:11,320 TREATMENT OF PATIENTS WITH 1187 00:46:11,320 --> 00:46:13,400 LYMPHOMAS, ALL STUDIES DONE BY 1188 00:46:13,400 --> 00:46:14,760 KITE PHARMA, IN THE SURGERY 1189 00:46:14,760 --> 00:46:16,920 BRANCH HERE WERE THE DIFFUSE 1190 00:46:16,920 --> 00:46:19,000 LARGE B CELL LYMPHOMAS, THE MOST 1191 00:46:19,000 --> 00:46:22,600 AGGRESSIVE AGGRESSIVE OF THE 1192 00:46:22,600 --> 00:46:23,480 LYMPHOMAS IN ADULTS. 1193 00:46:23,480 --> 00:46:25,000 MY CONGRATULATIONS TO THE 1194 00:46:25,000 --> 00:46:26,760 PHYSICIANS AND SCIENTISTS IN 1195 00:46:26,760 --> 00:46:27,840 PEDIATRIC ONCOLOGY BRANCH FOR 1196 00:46:27,840 --> 00:46:29,840 PIONEERING WORK TO BRING THE 1197 00:46:29,840 --> 00:46:36,640 CELL THERAPY TO PEDIATRIC 1198 00:46:36,640 --> 00:46:37,840 PATIENTS, PERFORMING OUTSTANDING 1199 00:46:37,840 --> 00:46:39,280 RESEARCH THAT REFINED THE 1200 00:46:39,280 --> 00:46:41,120 APPROACH AND IMPROVED THIS 1201 00:46:41,120 --> 00:46:43,200 LIVING DRUG TREATMENT FOR 1202 00:46:43,200 --> 00:46:46,360 PATIENTS AND FOR THAT THEY HAVE 1203 00:46:46,360 --> 00:46:47,560 MY ENDURING THANKS. 1204 00:46:47,560 --> 00:46:49,040 THANK YOU FOR YOUR KIND 1205 00:46:49,040 --> 00:46:49,560 ATTENTION. 1206 00:46:49,560 --> 00:46:51,960 [APPLAUSE] 1207 00:46:51,960 --> 00:46:58,000 1208 00:46:58,000 --> 00:46:59,600 1209 00:46:59,600 --> 00:47:01,360 >> NEXT SESSION, IF I COULD ASK 1210 00:47:01,360 --> 00:47:03,760 THE SPEAKERS TO MAKE THEIR WAY 1211 00:47:03,760 --> 00:47:07,280 DOWN, WE'LL START OFF WITH A 1212 00:47:07,280 --> 00:47:09,080 VIDEO WHICH WILL GO INTO THE 1213 00:47:09,080 --> 00:47:11,520 TALKING ABOUT CAR T CELLS AND 1214 00:47:11,520 --> 00:47:14,320 ALL OF THE CLINICAL AND RESEARCH 1215 00:47:14,320 --> 00:47:16,800 COLLABORATIONS THAT WE HAVE. 1216 00:47:16,800 --> 00:47:19,480 WE'LL START OFF WITH TREY LEE 1217 00:47:19,480 --> 00:47:20,960 WHO COULDN'T BE HERE IN PERSON, 1218 00:47:20,960 --> 00:47:24,160 HE'S ON SERVICE, WE'LL TAKE IT 1219 00:47:24,160 --> 00:47:25,800 WITH ANTHONY, SO FOLKS CAN MAKE 1220 00:47:25,800 --> 00:47:26,480 THEIR WAY DOWN. 1221 00:47:26,480 --> 00:47:28,960 THANK YOU. 1222 00:47:28,960 --> 00:47:33,520 1223 00:47:33,520 --> 00:47:36,640 >> I'M SORRY I COULDN'T BE WITH 1224 00:47:36,640 --> 00:47:37,160 YOU TODAY. 1225 00:47:37,160 --> 00:47:39,800 WHEN I WAS THERE MANY YEARS AGO 1226 00:47:39,800 --> 00:47:41,480 NOW, AS A NEW FELLOW LOOKING FOR 1227 00:47:41,480 --> 00:47:43,720 RESEARCH PROJECT, I WAS STRUCK 1228 00:47:43,720 --> 00:47:44,600 BY DR. ROSENBERG'S PRESENTATION 1229 00:47:44,600 --> 00:47:48,520 TO THE GROUP ONE DAY ABOUT 1230 00:47:48,520 --> 00:47:51,560 RESPONSES IN ADULTS WITH WIDELY 1231 00:47:51,560 --> 00:47:52,560 MEDICAL STATIC MELANOMA WITH ONE 1232 00:47:52,560 --> 00:47:55,640 OR TWO INFUSIONS OF CELLS, 1233 00:47:55,640 --> 00:47:56,800 BEFORE CHECKPOINT INHIBITORS, TO 1234 00:47:56,800 --> 00:47:58,520 ME IT WAS AMAZING. 1235 00:47:58,520 --> 00:48:00,600 I WANTED TO BRING THIS 1236 00:48:00,600 --> 00:48:04,320 GAME-CHANGING THERAPY TO KIDS 1237 00:48:04,320 --> 00:48:05,440 WITH RELAPSED REFRACTORY 1238 00:48:05,440 --> 00:48:06,920 CANCERS, FORTUNATE TO FIND 1239 00:48:06,920 --> 00:48:08,640 PARTNERS AND MENTORS IN CRYSTAL, 1240 00:48:08,640 --> 00:48:10,240 ALLEN AND TERRY WHO GUIDED ME 1241 00:48:10,240 --> 00:48:13,840 AND WE DID JUST THAT. 1242 00:48:13,840 --> 00:48:19,720 EARLY ON IN THE PEDIATRIC CAR 1243 00:48:19,720 --> 00:48:26,040 CAR T TRIAL, IT HELD FOR KIDS, 1244 00:48:26,040 --> 00:48:28,360 QUITE CLEAR, EVIDENT THE 1245 00:48:28,360 --> 00:48:30,760 LIFE-THREATENING TOXICITIES THEY 1246 00:48:30,760 --> 00:48:30,960 CAUSE. 1247 00:48:30,960 --> 00:48:33,760 WE KNEW ABOUT AND USED STEROIDS 1248 00:48:33,760 --> 00:48:37,800 IN PATIENTS BEFORE, WE DID NOT 1249 00:48:37,800 --> 00:48:39,320 KNOW IF INTERVENING WOULD ABORT 1250 00:48:39,320 --> 00:48:44,040 THE RESPONSE. 1251 00:48:44,040 --> 00:48:49,880 THE 14th PATIENT CHANGED THE 1252 00:48:49,880 --> 00:48:51,640 PERSPECTIVE. 1253 00:48:51,640 --> 00:48:54,360 CYTOKINE RELEASE SYNDROME RAGES 1254 00:48:54,360 --> 00:49:01,920 FROM FEVER TO TO PULMONARY 1255 00:49:01,920 --> 00:49:03,920 EDEMA, CARDIAC DYSFUNCTION AND 1256 00:49:03,920 --> 00:49:06,200 EVEN CARDIAC ARREST, DRIVEN BY 1257 00:49:06,200 --> 00:49:08,000 SUPER PHYSIOLOGIC PRODUCTION OF 1258 00:49:08,000 --> 00:49:08,800 MULTIPLE INFLAMMATORY CYTOKINES 1259 00:49:08,800 --> 00:49:11,200 OVER THE FIRST FEW DAYS AFTER 1260 00:49:11,200 --> 00:49:12,840 CELL INFUSION. 1261 00:49:12,840 --> 00:49:14,440 AFTER OUR EXPERIENCE WITH 1262 00:49:14,440 --> 00:49:17,680 PATIENT NUMBER 14 WHO SURVIVED, 1263 00:49:17,680 --> 00:49:20,640 THANKS TO THE AMAZING ICU TEAM 1264 00:49:20,640 --> 00:49:24,800 WE DEVELOPED THE FIRST 1265 00:49:24,800 --> 00:49:27,120 MANUSCRIPT DESCRIBING CRS, 1266 00:49:27,120 --> 00:49:27,760 RELEVANT RATING SYSTEM, 1267 00:49:27,760 --> 00:49:29,320 MANAGEMENT ALGORITHM TIED TO 1268 00:49:29,320 --> 00:49:30,200 THAT SYSTEM. 1269 00:49:30,200 --> 00:49:31,280 LITTLE DID WE KNOW THIS WORK 1270 00:49:31,280 --> 00:49:34,440 WOULD BECOME ONE OF THE WORLD'S 1271 00:49:34,440 --> 00:49:37,160 MOST WIDELY USED CLINICALLY AND 1272 00:49:37,160 --> 00:49:38,600 CITED MANUSCRIPTS FOR CRS, AND 1273 00:49:38,600 --> 00:49:45,360 TO SERVE AS PRECURSOR TO PRESENT 1274 00:49:45,360 --> 00:49:46,240 DAY ASTCT CRS. 1275 00:49:46,240 --> 00:49:47,880 WE HAVE SO MUCH MORE TO DO. 1276 00:49:47,880 --> 00:49:49,960 CARs IN THE CLINIC TODAY ARE 1277 00:49:49,960 --> 00:49:51,480 JUST THE PROTOTYPES, WE CAN DO 1278 00:49:51,480 --> 00:49:52,960 SO MUCH BETTER. 1279 00:49:52,960 --> 00:49:55,800 WE NEED TO BROADEN EFFECTIVE AND 1280 00:49:55,800 --> 00:49:59,400 SAFE CARs TO DISEASES BEYOND 1281 00:49:59,400 --> 00:50:00,600 HEMEOLOGIC MALIGNANCY. 1282 00:50:00,600 --> 00:50:05,200 THIS MY LAB'S AIM AT UNIVERSITY 1283 00:50:05,200 --> 00:50:07,400 OF VIRGINIA, TARGETING BETA 3 1284 00:50:07,400 --> 00:50:10,760 AND DEMONSTRATING EFFICACY IN 1285 00:50:10,760 --> 00:50:17,120 GLIOBLASTOMA AND DIPG, ACROSS 1286 00:50:17,120 --> 00:50:19,080 NUMEROUS TUMORS, AIMING TO MAKE 1287 00:50:19,080 --> 00:50:22,360 ALL CARs SAFER DEVELOPING 1288 00:50:22,360 --> 00:50:23,480 INTELLIGENT SELF-CONTAINED 1289 00:50:23,480 --> 00:50:26,320 CONTROL MECHANISMS THAT MITIGATE 1290 00:50:26,320 --> 00:50:28,040 TOXICITY, PRESERVING EFFICACY, 1291 00:50:28,040 --> 00:50:30,600 USING COMPLEMENTARY LABORATORY 1292 00:50:30,600 --> 00:50:32,120 AND BIOCOMPLEXITY APPROACHES TO 1293 00:50:32,120 --> 00:50:35,520 UNDERSTAND COMPLEX MECHANISMS 1294 00:50:35,520 --> 00:50:37,920 AND PATHWAYS FROM A CAR T CELL 1295 00:50:37,920 --> 00:50:48,400 THROUGH TO SEVERE CRS, HLH, 1296 00:50:52,440 --> 00:50:52,600 ICANs. 1297 00:50:52,600 --> 00:50:53,920 WE HAVE ACCOMPLISHED SO MUCH FOR 1298 00:50:53,920 --> 00:50:55,440 KIDS WITH LEUKEMIA AND LYMPHOMA, 1299 00:50:55,440 --> 00:50:58,040 THIS IS JUST THE BEGINNING, AN 1300 00:50:58,040 --> 00:50:59,480 EXCITING TIME BECAUSE I'M 1301 00:50:59,480 --> 00:51:01,880 CONVINCED IN YEARS TO COME THE 1302 00:51:01,880 --> 00:51:04,320 CAR T FIELD WILL EVOLVE 1303 00:51:04,320 --> 00:51:04,960 EXPONENTIALLY, TRANSFORMING 1304 00:51:04,960 --> 00:51:06,640 OUTCOMES FOR SO MANY PEDIATRIC 1305 00:51:06,640 --> 00:51:07,720 CANCERS ALONG THE WAY. 1306 00:51:07,720 --> 00:51:09,320 IT'S BEEN SUCH AN HONOR TO HAVE 1307 00:51:09,320 --> 00:51:10,120 WORKED WITH YOU ALL. 1308 00:51:10,120 --> 00:51:13,280 THANK YOU VERY MUCH. 1309 00:51:13,280 --> 00:51:19,320 1310 00:51:19,320 --> 00:51:23,440 1311 00:51:23,440 --> 00:51:25,600 1312 00:51:25,600 --> 00:51:27,560 >> IF WE COULD GO TO THE SLIDE 1313 00:51:27,560 --> 00:51:29,840 DECK. 1314 00:51:29,840 --> 00:51:35,840 1315 00:51:35,840 --> 00:51:39,360 1316 00:51:39,360 --> 00:51:41,640 IT WILL BE A SERIES OF TALKS. 1317 00:51:41,640 --> 00:51:46,200 WE'LL HAVE YOU GO AHEAD. 1318 00:51:46,200 --> 00:51:46,560 1319 00:51:46,560 --> 00:51:49,200 >> THANK YOU VERY MUCH. 1320 00:51:49,200 --> 00:51:51,960 I THINK FROM THE ICUs 1321 00:51:51,960 --> 00:51:52,800 PERSPECTIVE WE'RE FORTUNATE OR 1322 00:51:52,800 --> 00:51:55,000 PRIVILEGED I WOULD SAY TO BE 1323 00:51:55,000 --> 00:51:56,840 ABLE TO PARTICIPATE IN REALLY 1324 00:51:56,840 --> 00:51:58,240 LIFE-CHANGING CARE THAT IS BEING 1325 00:51:58,240 --> 00:52:02,120 DEVELOPED IN THE CLINICAL 1326 00:52:02,120 --> 00:52:02,400 CENTER. 1327 00:52:02,400 --> 00:52:05,200 SO, HOW DOES THIS RELATE TO 1328 00:52:05,200 --> 00:52:06,280 CRITICAL ILLNESS? 1329 00:52:06,280 --> 00:52:07,360 YOU HEARD ABOUT THE CYTOKINE 1330 00:52:07,360 --> 00:52:09,320 STORM, WHY IS IT RELEVANT TO 1331 00:52:09,320 --> 00:52:10,680 CRITICAL CARE? 1332 00:52:10,680 --> 00:52:15,560 THE CYTOKINE RELEASE SYNDROME 1333 00:52:15,560 --> 00:52:20,520 LEADS TO INFLAMMATORY ORGAN 1334 00:52:20,520 --> 00:52:30,640 CAUSING HYPOTENSION, SHOCK, 1335 00:52:30,640 --> 00:52:31,200 RESPIRATORY FAILURE, 1336 00:52:31,200 --> 00:52:31,920 ENENCEPHALOPARITY, ARE THERE 1337 00:52:31,920 --> 00:52:33,640 WAYS TO PREVENT THIS? 1338 00:52:33,640 --> 00:52:39,080 PERHAPS, INCLUDING THE 1339 00:52:39,080 --> 00:52:40,200 UNDERLYING PULMONARY DISEASE, 1340 00:52:40,200 --> 00:52:43,040 HOW FRAGILE THE PATIENT IS, 1341 00:52:43,040 --> 00:52:43,920 DISEASE BURDEN, CELL PRODUCT 1342 00:52:43,920 --> 00:52:46,560 THEY ARE RECEIVING, SPECIFIC 1343 00:52:46,560 --> 00:52:48,520 LIVE INFECTION PROPHYLAXIS 1344 00:52:48,520 --> 00:52:52,560 AGAINST FUNGI, AGAINST BACTERIA, 1345 00:52:52,560 --> 00:52:55,320 ATTENTION TO BE VERY AGGRESSIVE 1346 00:52:55,320 --> 00:52:58,520 ABOUT DIAGNOSING AND TREATING 1347 00:52:58,520 --> 00:53:03,480 INFECTION, THE NIGHTMARE TREY 1348 00:53:03,480 --> 00:53:06,160 DESCRIBED, ON DAY 7 AS HE 1349 00:53:06,160 --> 00:53:08,360 RECEIVED CELLS, AFTER HE 1350 00:53:08,360 --> 00:53:14,320 DEVELOPED ACUTE PULMONARY 1351 00:53:14,320 --> 00:53:15,720 EDEMA, AND CARDIOGENIC SHOCK. 1352 00:53:15,720 --> 00:53:18,200 ECHO SHOWN HERE ON THE LEFT 1353 00:53:18,200 --> 00:53:18,960 SIDE, PRE-ARREST, ON THE RIGHT 1354 00:53:18,960 --> 00:53:21,240 SIDE YOU CAN SEE HIS LEFT 1355 00:53:21,240 --> 00:53:22,720 VENTRICLE IS BARELY MOVING. 1356 00:53:22,720 --> 00:53:28,640 HE WALS -- WAS IN PROFOUND 1357 00:53:28,640 --> 00:53:32,000 SHOCK, A DISASTER IN THE ICU, 1358 00:53:32,000 --> 00:53:36,040 RELATED TO CYTOKINE RELEASE, 1359 00:53:36,040 --> 00:53:38,680 CARDIAC ARREST, PROLONGED CPR, 1360 00:53:38,680 --> 00:53:39,800 WHEN I SAY PROLONGED, 3 1/2 1361 00:53:39,800 --> 00:53:42,440 HOURS OF ON AND OFF HAVING TO DO 1362 00:53:42,440 --> 00:53:46,320 CHEST COMPRESSIONS ON THIS YOUNG 1363 00:53:46,320 --> 00:53:51,280 PERSON, CARDIOGENIC SHOCK, ARDS, 1364 00:53:51,280 --> 00:53:54,320 TREATED WITH FLUIDS, 1365 00:53:54,320 --> 00:53:55,640 VASOPRESSORS, INOTROPES, AND A 1366 00:53:55,640 --> 00:53:59,240 BALLOON PUMP TO HELP HIS HEART 1367 00:53:59,240 --> 00:54:01,440 SURVIVE, GIVEN ANTI-INFLAMMATORY 1368 00:54:01,440 --> 00:54:03,160 THERAPY WITH STEROIDS, ANTI-IL-6 1369 00:54:03,160 --> 00:54:03,760 THERAPY. 1370 00:54:03,760 --> 00:54:05,360 WHAT IS NOTABLE AFTER EIGHT DAYS 1371 00:54:05,360 --> 00:54:09,440 HE LEFT THE HOSPITAL, LEFT THE 1372 00:54:09,440 --> 00:54:11,520 ICU, AFTER A COMPLEX COURSE, 1373 00:54:11,520 --> 00:54:12,720 GREAT COOPERATION AND 1374 00:54:12,720 --> 00:54:14,240 COLLABORATION BETWEEN HEM-ONC 1375 00:54:14,240 --> 00:54:17,640 TEAMS AND ICU, WENT HOME. 1376 00:54:17,640 --> 00:54:19,760 THIS IS THE MOST SEVERE SENSE, 1377 00:54:19,760 --> 00:54:21,280 THE WORST CASE SCENARIO. 1378 00:54:21,280 --> 00:54:22,600 AS TREY WAS MENTIONING, HOW DO 1379 00:54:22,600 --> 00:54:23,360 YOU AVOID IT? 1380 00:54:23,360 --> 00:54:25,760 ONE OF THE WAYS IS YOU COME UP 1381 00:54:25,760 --> 00:54:29,160 WITH THESE GRADES, THIS IDEA, AS 1382 00:54:29,160 --> 00:54:29,800 THE INFLAMMATORY RESPONSE 1383 00:54:29,800 --> 00:54:32,520 ESCALATES WHAT CAN YOU DO TO 1384 00:54:32,520 --> 00:54:35,040 INTERVENE AND TO NOT HAVE THESE 1385 00:54:35,040 --> 00:54:35,600 THINGS DETERIORATE? 1386 00:54:35,600 --> 00:54:38,000 THIS IS SOME OF THE THINGS HE 1387 00:54:38,000 --> 00:54:40,400 WAS DISCUSSING, THE GRADE 1 1388 00:54:40,400 --> 00:54:41,680 THROUGH 4 TOXICITY BASED ON LOW 1389 00:54:41,680 --> 00:54:44,280 BLOOD PRESSURE, HOW DO YOU TREAT 1390 00:54:44,280 --> 00:54:47,600 IT, BASED UPON HYPOXIA, AND THE 1391 00:54:47,600 --> 00:54:51,240 SAME SCALES USED FOR 1392 00:54:51,240 --> 00:54:51,760 ENCEPHALOPATHY SYNDROME, 1393 00:54:51,760 --> 00:54:59,960 PATIENTS WHO GET CAR CELLS CAN 1394 00:54:59,960 --> 00:55:05,760 BE CONFUSED, DELIRIOUS, 1395 00:55:05,760 --> 00:55:06,080 UNAROUSABLE. 1396 00:55:06,080 --> 00:55:12,160 SEIZURES, MOTOR WEAKNESS, 1397 00:55:12,160 --> 00:55:13,800 ELEVATED INTRACRANIAL PRESSURE, 1398 00:55:13,800 --> 00:55:14,880 INTERVENING SO YOU DON'T LET 1399 00:55:14,880 --> 00:55:16,360 THINGS GET OUT OF HAND LIKE THE 1400 00:55:16,360 --> 00:55:19,000 CASE I SHOWED YOU. 1401 00:55:19,000 --> 00:55:22,440 FROM THE ICU'S PERSPECTIVE, OUR 1402 00:55:22,440 --> 00:55:24,240 MANAGEMENT STRATEGY TO INTERVENE 1403 00:55:24,240 --> 00:55:27,800 EARLY, GRADE 2 AND 3 WITH ORGAN 1404 00:55:27,800 --> 00:55:35,000 SPECIFIC THERAPY AS LISTED 1405 00:55:35,000 --> 00:55:36,800 THERE, SO YOU CAN SEE AROUND THE 1406 00:55:36,800 --> 00:55:39,960 WORLD RIGHT NOW IN TERMS OF SOME 1407 00:55:39,960 --> 00:55:41,960 THERAPIES DEVELOPED HERE HAVE 1408 00:55:41,960 --> 00:55:45,800 EXPLODED ACROSS THE WORLD. 1409 00:55:45,800 --> 00:55:49,120 THIS IS STUDY THAT JUST CAME OUT 1410 00:55:49,120 --> 00:55:51,560 IN 2021 WAS NOTABLE FOR 922 1411 00:55:51,560 --> 00:55:52,600 PATIENTS TREATED AROUND THE 1412 00:55:52,600 --> 00:55:54,720 WORLD, ASKING WHAT IS THE 1413 00:55:54,720 --> 00:55:56,560 CRITICAL CARE OUTCOME. 1414 00:55:56,560 --> 00:55:57,560 NIRALI AND JOHN FROM OUR 1415 00:55:57,560 --> 00:55:59,280 DEPARTMENT WROTE A FLIES 1416 00:55:59,280 --> 00:56:00,840 EDITORIAL, THERE'S ANOTHER STUDY 1417 00:56:00,840 --> 00:56:03,240 THAT RECENTLY CAME OUT AGAIN 1418 00:56:03,240 --> 00:56:05,000 ADDRESSING THE COMPLEXITY OF 1419 00:56:05,000 --> 00:56:06,440 CRITICAL CARE ILLNESS THAT 1420 00:56:06,440 --> 00:56:08,040 DEVELOPS AFTER CAR T CELL 1421 00:56:08,040 --> 00:56:08,360 THERAPIES. 1422 00:56:08,360 --> 00:56:11,960 WHEN IT HAPPENS, WHAT TO DO, HOW 1423 00:56:11,960 --> 00:56:15,600 TO STRATEGIZE TO MINIMIZE THE 1424 00:56:15,600 --> 00:56:21,200 CONSEQUENCES AND THE END ORGAN 1425 00:56:21,200 --> 00:56:21,600 INJURIES. 1426 00:56:21,600 --> 00:56:29,440 I'LL END WITH A QUOTE FROM 1427 00:56:29,440 --> 00:56:38,400 NIRALI, DUE TO THE RISKS OF 1428 00:56:38,400 --> 00:56:40,600 ICANS, ICU IS PARTNERS IN THE 1429 00:56:40,600 --> 00:56:43,160 DELIVERY OF LIFE-SAVING 1430 00:56:43,160 --> 00:56:47,360 PARTNERS. PART -- LIFE SAVING 1431 00:56:47,360 --> 00:56:47,760 THERAPY. 1432 00:56:47,760 --> 00:56:52,560 THANKS VERY MUCH. 1433 00:56:52,560 --> 00:56:54,600 1434 00:56:54,600 --> 00:56:56,800 [APPLAUSE] 1435 00:56:56,800 --> 00:57:02,840 1436 00:57:02,840 --> 00:57:06,000 1437 00:57:06,000 --> 00:57:09,640 >> I'M HERE TO TALK ABOUT CAR T 1438 00:57:09,640 --> 00:57:12,160 CELL ASSOCIATED NEUROTOXICITY, 1439 00:57:12,160 --> 00:57:19,440 I'M HANEEN, A PEDIATRIC LEUKEMIA 1440 00:57:19,440 --> 00:57:20,360 DOCTOR. 1441 00:57:20,360 --> 00:57:21,760 NEUROTOXICITY SYNDROME, ICANS, 1442 00:57:21,760 --> 00:57:23,280 IS A NEUROLOGIC DISORDER 1443 00:57:23,280 --> 00:57:25,040 FOLLOWING IMMUNE THERAPY THAT 1444 00:57:25,040 --> 00:57:28,120 RESULTS IN THE ACTIVATION OF 1445 00:57:28,120 --> 00:57:30,000 IMMUNE EFFECTOR CELLS, INCIDENCE 1446 00:57:30,000 --> 00:57:35,680 RANGE FROM ZERO TO 64%, SEVERE 1447 00:57:35,680 --> 00:57:38,440 ICANS AS GRADED OCCURRED IN FIVE 1448 00:57:38,440 --> 00:57:41,160 TO 50% OF PATIENTS TREATED. 1449 00:57:41,160 --> 00:57:42,520 PRESENTING SYMPTOMS AND TIMING 1450 00:57:42,520 --> 00:57:45,680 OF SYMPTOMS VARIES. 1451 00:57:45,680 --> 00:57:46,760 TYPICALLY OCCURS AFTER CYTOKINE 1452 00:57:46,760 --> 00:57:49,920 RELEASE SYNDROME, SIGNS AND 1453 00:57:49,920 --> 00:57:53,400 SYMPTOMS CAN INCLUDE CONFUSION, 1454 00:57:53,400 --> 00:58:00,840 APHAGIA, DYSGRAPHIA, DELIRIUM. 1455 00:58:00,840 --> 00:58:02,000 MECHANISMS CONTRIBUTE, RESEARCH 1456 00:58:02,000 --> 00:58:06,440 IS UNDERWAY TO PINPOINT WHAT 1457 00:58:06,440 --> 00:58:10,840 OCCURS WITH THERAPY. 1458 00:58:10,840 --> 00:58:11,640 ENDOTHELIAL DYSREGULATION OCCURS 1459 00:58:11,640 --> 00:58:17,640 IN SOME OF THE PATIENTS WE'VE 1460 00:58:17,640 --> 00:58:17,840 SEEN. 1461 00:58:17,840 --> 00:58:20,480 WHAT WE'VE LEARNED OVER THE LAST 1462 00:58:20,480 --> 00:58:23,000 DECADE IS THAT WE'VE HAD 1463 00:58:23,000 --> 00:58:26,080 SIGNIFICANT AMOUNT OF PATIENT 1464 00:58:26,080 --> 00:58:27,160 EXPERIENCE AND THANKFULLY HAVE 1465 00:58:27,160 --> 00:58:30,760 SEEN NO INCREASED RATES OF ICANS 1466 00:58:30,760 --> 00:58:32,320 IN TRIALS. 1467 00:58:32,320 --> 00:58:34,000 IN CD19 TRIAL WE WERE ABLE TO 1468 00:58:34,000 --> 00:58:36,000 DEMONSTRATE THAT WE WERE ABLE TO 1469 00:58:36,000 --> 00:58:37,600 GIVE THIS THERAPY SAFELY TO 1470 00:58:37,600 --> 00:58:39,440 PEDIATRIC AND YOUNG ADULT 1471 00:58:39,440 --> 00:58:40,640 PATIENTS INCLUDING PATIENTS WITH 1472 00:58:40,640 --> 00:58:41,720 ACTIVE CNS DISEASE, THIS WAS ONE 1473 00:58:41,720 --> 00:58:44,680 OF THE FIRST STUDIES THAT 1474 00:58:44,680 --> 00:58:46,440 ALLOWED FOR ENROLLMENT OF 1475 00:58:46,440 --> 00:58:49,640 PATIENT WITH CENTRAL NERVOUS 1476 00:58:49,640 --> 00:58:51,680 SYSTEM LEUKEMIA. 1477 00:58:51,680 --> 00:58:52,960 ICASNS WAS ASSOCIATED WITH 1478 00:58:52,960 --> 00:58:54,160 CYTOKINE RELEASE SYNDROME, DID 1479 00:58:54,160 --> 00:58:56,160 NOT SEE INCREASED RISK IN 1480 00:58:56,160 --> 00:58:58,520 PATIENTS WITH ACTIVE CNS 1481 00:58:58,520 --> 00:58:59,000 DISEASE. 1482 00:58:59,000 --> 00:59:00,640 VERY IMPORTANTLY, BUT OBVIOUSLY 1483 00:59:00,640 --> 00:59:02,280 NOW A DECADE LATER, THIS IS 1484 00:59:02,280 --> 00:59:03,160 SHOWN MULTIPLE TIMES, BUT AT THE 1485 00:59:03,160 --> 00:59:05,480 TIME WAS VERY NOVEL THAT CAR T 1486 00:59:05,480 --> 00:59:06,680 CELLS DID TRAFFIC EFFECTIVELY TO 1487 00:59:06,680 --> 00:59:09,240 THE CNS AND WAS ABLE TO 1488 00:59:09,240 --> 00:59:10,480 ERADICATE DISEASE. 1489 00:59:10,480 --> 00:59:12,680 WITH THE CD22 CAR TRIAL WERE 1490 00:59:12,680 --> 00:59:17,720 ABLE TO DEMONSTRATE EFFICACY, AS 1491 00:59:17,720 --> 00:59:22,080 A SALVAGE THERAPY ERADICATING 1492 00:59:22,080 --> 00:59:22,800 LEUKEMIA WHO RELAPSED. 1493 00:59:22,800 --> 00:59:25,680 RATES WERE LOW AND DIDN'T SEE 1494 00:59:25,680 --> 00:59:26,320 IRREVERSIBLE NEUROTOXICITY. 1495 00:59:26,320 --> 00:59:28,880 WITH THIS WERE ABLE TO 1496 00:59:28,880 --> 00:59:29,720 DEMONSTRATE FEASIBILITY OF 1497 00:59:29,720 --> 00:59:32,360 SYSTEMATIC ASSESSMENTS IN OUR 1498 00:59:32,360 --> 00:59:35,440 PATIENTS WHICH INCLUDED IMAGING, 1499 00:59:35,440 --> 00:59:36,080 CYTOKINE SAMPLING, 1500 00:59:36,080 --> 00:59:36,760 NEUROCOGNITIVE ASSESSMENTS WHICH 1501 00:59:36,760 --> 00:59:38,600 YOU'LL HEAR NEXT AND CAREGIVER 1502 00:59:38,600 --> 00:59:40,520 SYMPTOM CHECK LIST BORN IN THE 1503 00:59:40,520 --> 00:59:41,560 PEDIATRIC ONCOLOGY BRANCH. 1504 00:59:41,560 --> 00:59:45,480 WITH OUR MOST RECENT PROTOCOL, 1505 00:59:45,480 --> 00:59:47,800 THE CD19, CD22 CAR T CELL TRIAL 1506 00:59:47,800 --> 00:59:51,960 DEMONSTRATED THEY WERE WELL 1507 00:59:51,960 --> 00:59:52,240 TOLERATED. 1508 00:59:52,240 --> 00:59:58,400 WE HAD A LOW RATE OF ICANS, 1509 00:59:58,400 --> 00:59:59,600 DEMONSTRATING INTRATHECAL 1510 00:59:59,600 --> 01:00:03,440 HYDROCORTISONE WAS SUCCESSFUL IN 1511 01:00:03,440 --> 01:00:11,560 REVERSING A PATIENT WITH SEVERE 1512 01:00:11,560 --> 01:00:11,960 ICANS. 1513 01:00:11,960 --> 01:00:17,680 IT BUILT THE FOUNDATION TO 1514 01:00:17,680 --> 01:00:19,760 PERFORM REMOTE TESTING. 1515 01:00:19,760 --> 01:00:20,480 WITH ICANS SIGNIFICANT QUESTIONS 1516 01:00:20,480 --> 01:00:21,960 REMAIN IN THE FIELD. 1517 01:00:21,960 --> 01:00:24,440 ARE WE ABLE TO PREDICT PATIENTS 1518 01:00:24,440 --> 01:00:26,000 WHO WILL HAVE SEVERE ICANS, DO 1519 01:00:26,000 --> 01:00:27,440 WE HAVE GOOD TREATMENT OPTIONS, 1520 01:00:27,440 --> 01:00:31,480 IF SO WHAT'S THE BEST TREATMENT? 1521 01:00:31,480 --> 01:00:35,320 DOES NEUROIMAGING AT BASELINE 1522 01:00:35,320 --> 01:00:38,480 PREDICT ICANS AND DOES IT 1523 01:00:38,480 --> 01:00:39,840 AEFFECT LONG-TERM OUTCOME? 1524 01:00:39,840 --> 01:00:42,560 THROUGH THE WORK WERE ABLE TO 1525 01:00:42,560 --> 01:00:43,240 ESTABLISH MULTI-SITE 1526 01:00:43,240 --> 01:00:45,080 COLLABORATIONS, HOSTED A BEYOND 1527 01:00:45,080 --> 01:00:47,040 THE STORM MEETING, A COUPLE 1528 01:00:47,040 --> 01:00:47,680 YEARS AGO. 1529 01:00:47,680 --> 01:00:49,840 THROUGH THAT WAS BORN A LARGE 1530 01:00:49,840 --> 01:00:52,960 NETWORK OF PROVIDERS IN THE 1531 01:00:52,960 --> 01:00:54,440 PEDIATRIC ONCOLOGY CAR T CELL 1532 01:00:54,440 --> 01:00:54,880 COMMUNITY. 1533 01:00:54,880 --> 01:01:02,240 NOW WE HAVE A STUDY LOOKING AT 1534 01:01:02,240 --> 01:01:03,240 OUTCOMES AT THREE SITES HOPING 1535 01:01:03,240 --> 01:01:10,240 TO OPEN IN THE FALL, 1536 01:01:10,240 --> 01:01:11,000 ASSOCIATIONS. 1537 01:01:11,000 --> 01:01:14,280 WE'RE PART OF A STUDY WITH 1538 01:01:14,280 --> 01:01:16,440 SEATTLE CHILDREN'S AND ST. JUDE 1539 01:01:16,440 --> 01:01:19,320 LOOKING AT QUALITY OF LIFE POST 1540 01:01:19,320 --> 01:01:22,480 THERAPY WITH SEATTLE CHILDREN'S 1541 01:01:22,480 --> 01:01:24,920 AND CHLA EMBARKED ON A 1542 01:01:24,920 --> 01:01:28,080 COLLABORATION TO CREATE A 1543 01:01:28,080 --> 01:01:30,600 VIRTUAL ARCHIVE LESION PROTOCOL 1544 01:01:30,600 --> 01:01:34,240 TO BANK THE MRIs SO WE CAN 1545 01:01:34,240 --> 01:01:36,520 EVALUATE AND CATEGORIZE 1546 01:01:36,520 --> 01:01:39,480 NEUROIMAGING FINDINGS POST CAR, 1547 01:01:39,480 --> 01:01:42,000 DESCRIBE PATTERNS OF 1548 01:01:42,000 --> 01:01:45,920 ABNORMALITIES DURING ICANS, 1549 01:01:45,920 --> 01:01:47,160 BUILDING A FOLLOW-UP PROTOCOL 1550 01:01:47,160 --> 01:01:49,240 FOR LATE EFFECTS. 1551 01:01:49,240 --> 01:01:51,560 WITH THIS, I HOPE YOU HAVE 1552 01:01:51,560 --> 01:01:53,200 REALIZED THE HARD WORK OVER THE 1553 01:01:53,200 --> 01:01:54,840 LAST DECADE, ALSO NOTE WE HAVE 1554 01:01:54,840 --> 01:01:56,040 SO MUCH MORE WORK TO DO. 1555 01:01:56,040 --> 01:01:58,280 I THANK YOU FOR YOUR TIME. 1556 01:01:58,280 --> 01:02:00,320 [APPLAUSE] 1557 01:02:00,320 --> 01:02:02,040 >>BEFORE I GET STARTED, I WANT 1558 01:02:02,040 --> 01:02:03,840 TO SAY THERE'S NO WAY IN THREE 1559 01:02:03,840 --> 01:02:05,560 MINUTES I COULD BE ABLE TO 1560 01:02:05,560 --> 01:02:06,560 ADDRESS THE HONOR AND GIFT IT'S 1561 01:02:06,560 --> 01:02:08,680 BEEN TO BE ABLE TO BE PART OF 1562 01:02:08,680 --> 01:02:11,040 THIS PROJECT AND TO WORK WITH 1563 01:02:11,040 --> 01:02:12,720 THE MOST AMAZING PATIENTS AND 1564 01:02:12,720 --> 01:02:16,120 FAMILIES. 1565 01:02:16,120 --> 01:02:18,840 WHICH IS THE SLIDE THAT GOES 1566 01:02:18,840 --> 01:02:21,120 FORWARD, THIS ONE? 1567 01:02:21,120 --> 01:02:26,400 OKAY. 1568 01:02:26,400 --> 01:02:28,920 WELL, AS YOU'VE HEARD, CAR T 1569 01:02:28,920 --> 01:02:30,640 CELL THERAPY PROVIDES PROMISE 1570 01:02:30,640 --> 01:02:32,840 AND HOPE FOR PATIENTS WITH B 1571 01:02:32,840 --> 01:02:40,720 CELL MALIGNANCIES RESISTANT TO 1572 01:02:40,720 --> 01:02:41,720 TRADITIONAL TREATMENT. 1573 01:02:41,720 --> 01:02:45,000 YOU'VE HEARD ABOUT SIGNIFICANT 1574 01:02:45,000 --> 01:02:45,880 TOXICITIES, COMING WITH 1575 01:02:45,880 --> 01:02:51,680 UNCERTAIN PROGRESS PROGNOSIS 1576 01:02:51,680 --> 01:02:52,960 AND OUTCOME. 1577 01:02:52,960 --> 01:02:54,320 FAMILIES ARE LEAVING THEIR 1578 01:02:54,320 --> 01:02:59,880 PRIMARY SITE, PEOPLE WHO KNOW 1579 01:02:59,880 --> 01:03:01,960 THEM, PEOPLE THEY ARE 1580 01:03:01,960 --> 01:03:02,680 COMFORTABLE WITH, STARTING 1581 01:03:02,680 --> 01:03:05,360 OVERING NOT KNOWING IF THEY ARE 1582 01:03:05,360 --> 01:03:06,480 ELIGIBLE FOR THERAPY, LITTLE 1583 01:03:06,480 --> 01:03:08,200 THINGS, HOW A LINE CAN BE 1584 01:03:08,200 --> 01:03:09,240 ACCESSIONED IN A DIFFERENT WAY 1585 01:03:09,240 --> 01:03:13,720 CAN BE TRAUMATIC, COMPLEX FOR 1586 01:03:13,720 --> 01:03:15,560 THE PATIENT AND STAFF. 1587 01:03:15,560 --> 01:03:22,240 WE REALIZE THERE NEEDS TO BE A 1588 01:03:22,240 --> 01:03:25,320 STANDIZED WAY TO TAKE CARE OF 1589 01:03:25,320 --> 01:03:27,280 THE NEEDS OF THE PATIENTS BEYOND 1590 01:03:27,280 --> 01:03:28,720 MEDICAL OUTCOMES. 1591 01:03:28,720 --> 01:03:30,440 WE ASKED TO BE ABLE TO TALK 1592 01:03:30,440 --> 01:03:33,680 ABOUT ACCOMPLISHMENTS. 1593 01:03:33,680 --> 01:03:34,920 YOU'VE SEEN THESE EARLIER. 1594 01:03:34,920 --> 01:03:37,680 HOW DO WE PROVIDE PSYCHOSOCIAL 1595 01:03:37,680 --> 01:03:38,440 CARE FOR CHILDREN UNDERGOING CAR 1596 01:03:38,440 --> 01:03:39,440 T THERAPY? 1597 01:03:39,440 --> 01:03:42,400 TO BE ABLE TO FIND A WAY THAT 1598 01:03:42,400 --> 01:03:43,880 COULD BE MORE SYSTEMATIC. 1599 01:03:43,880 --> 01:03:45,640 THIS BEGINS RIGHT WHEN THEY 1600 01:03:45,640 --> 01:03:47,960 ARRIVED, EVEN BEFORE WHEN THEY 1601 01:03:47,960 --> 01:03:49,480 ARE GETTING APHERESIS, BEFORE 1602 01:03:49,480 --> 01:03:51,320 TREATMENT STARTS, AS WELL AS 1603 01:03:51,320 --> 01:03:54,720 DURING TREATMENT, AND AFTER 1604 01:03:54,720 --> 01:03:55,160 TREATMENT. 1605 01:03:55,160 --> 01:03:58,000 IT WAS REALLY EXCITING TO 1606 01:03:58,000 --> 01:04:00,080 PARTICIPATE IN THE FIRST PAPER 1607 01:04:00,080 --> 01:04:02,960 ON FERTILITY POST CAR T THERAPY. 1608 01:04:02,960 --> 01:04:03,680 TOM, IF YOU'RE WATCHING, THANK 1609 01:04:03,680 --> 01:04:05,000 YOU VERY MUCH. 1610 01:04:05,000 --> 01:04:06,960 THE FIRST CAR T ROAD TRIP WE 1611 01:04:06,960 --> 01:04:09,440 WANT TO BE ABLE TO HELP PATIENTS 1612 01:04:09,440 --> 01:04:12,000 WHEN THEY COME TO BE PREPARED, 1613 01:04:12,000 --> 01:04:16,080 TO HAVE A SENSE OF EMPOWERMENT, 1614 01:04:16,080 --> 01:04:17,400 OWNERSHIP, UNDERSTANDING. 1615 01:04:17,400 --> 01:04:19,560 THAT'S OUR DESI, PLAYING THE 1616 01:04:19,560 --> 01:04:20,640 GAME. 1617 01:04:20,640 --> 01:04:23,400 WE HAD A FIRST CAR T CELL SOCIAL 1618 01:04:23,400 --> 01:04:23,640 STORY. 1619 01:04:23,640 --> 01:04:25,280 IT'S AN ACTUAL BOOK THAT THE 1620 01:04:25,280 --> 01:04:27,560 CHILDREN WILL GET, WHERE THEY 1621 01:04:27,560 --> 01:04:28,960 CAN BE ABLE TO WRITE THEIR NAME 1622 01:04:28,960 --> 01:04:30,840 AND SEE EVERYTHING THAT WILL 1623 01:04:30,840 --> 01:04:33,240 TAKE PLACE THROUGHOUT THEIR 1624 01:04:33,240 --> 01:04:34,320 TREATMENT JOURNEY. 1625 01:04:34,320 --> 01:04:35,720 WE CAPTURED THE PATIENT'S 1626 01:04:35,720 --> 01:04:38,360 PERSPECTIVE, NOT JUST THE 1627 01:04:38,360 --> 01:04:40,640 MEDICAL OBJECTIVE PERSPECTIVES, 1628 01:04:40,640 --> 01:04:43,520 AND YOU HEARD FROM HANEEN WHAT 1629 01:04:43,520 --> 01:04:45,920 WE'RE COLLECTING, THE PATIENT'S 1630 01:04:45,920 --> 01:04:47,000 PERSPECTIVE OF THE SYMPTOMS THEY 1631 01:04:47,000 --> 01:04:49,320 ARE EXPERIENCING THROUGH THE 1632 01:04:49,320 --> 01:04:51,200 CD33, CHOP, AND FROM SEATTLE. 1633 01:04:51,200 --> 01:04:56,280 LOOKING AT QUALITY OF LIFE, 1634 01:04:56,280 --> 01:04:58,640 DECISIONS, QUANTITATIVE AND 1635 01:04:58,640 --> 01:04:58,920 QUALITATIVE. 1636 01:04:58,920 --> 01:05:00,360 QUALITATIVE INTERVIEWS POST CAR 1637 01:05:00,360 --> 01:05:02,000 T ARE REALLY INSTRUCTIVE AND 1638 01:05:02,000 --> 01:05:05,720 TELL US ABOUT THE EXPERIENCE. 1639 01:05:05,720 --> 01:05:10,920 SO WHERE DO WE GO? 1640 01:05:10,920 --> 01:05:15,800 WE WANT TO ASSESS SHORT- AND 1641 01:05:15,800 --> 01:05:16,920 LONG-TERM SOCIAL EFFECTS 1642 01:05:16,920 --> 01:05:19,400 INCLUDING FINANCIAL IMPACT WHICH 1643 01:05:19,400 --> 01:05:20,480 CAN BE SIGNIFICANT. 1644 01:05:20,480 --> 01:05:21,600 NOT ONLY FOR THE PATIENT, IT'S 1645 01:05:21,600 --> 01:05:28,160 SO IMPORTANT TO UNDERSTAND FOR 1646 01:05:28,160 --> 01:05:28,960 THE CAREGIVER, SIBLINGS. 1647 01:05:28,960 --> 01:05:30,800 WE WANT EVERY CENTER TO HAVE A 1648 01:05:30,800 --> 01:05:32,880 COPY OF THIS, TAILORED TO THEIR 1649 01:05:32,880 --> 01:05:34,080 OTHER THAN INDIVIDUAL PLACE, WE 1650 01:05:34,080 --> 01:05:36,120 WANT TO WORK TOWARDS AGREEMENT 1651 01:05:36,120 --> 01:05:39,440 ON RECOMMENDATION ON THOSE 1652 01:05:39,440 --> 01:05:40,520 PATIENT-REPORTED OUTCOMES SO WE 1653 01:05:40,520 --> 01:05:42,040 HAVE DIFFERENT SITES AND 1654 01:05:42,040 --> 01:05:43,280 DIFFERENT TIME POINTS CONSISTENT 1655 01:05:43,280 --> 01:05:45,400 BETWEEN ALL THE TRIALS TAKING 1656 01:05:45,400 --> 01:05:46,640 PLACE ACROSS THE WORLD. 1657 01:05:46,640 --> 01:05:48,720 WE WANT TO CONTINUE TO 1658 01:05:48,720 --> 01:05:50,400 COLLABORATE FOR A SMOOTH 1659 01:05:50,400 --> 01:05:51,920 TRANSITION, FROM WHEREVER YOU'RE 1660 01:05:51,920 --> 01:05:53,560 COMING FROM TO COMING HERE TO GO 1661 01:05:53,560 --> 01:05:56,200 BACK TO YOUR TREATMENT CENTERS, 1662 01:05:56,200 --> 01:05:57,320 REGARDLESS OF TREATMENT OUTCOME. 1663 01:05:57,320 --> 01:05:59,440 THANK YOU. 1664 01:05:59,440 --> 01:06:01,640 [APPLAUSE] 1665 01:06:01,640 --> 01:06:07,680 1666 01:06:07,680 --> 01:06:11,000 1667 01:06:11,000 --> 01:06:14,080 >> HI, I'M BONNIE YATES, NURSE 1668 01:06:14,080 --> 01:06:15,520 PRACTITIONERS WORKING WITH THE 1669 01:06:15,520 --> 01:06:16,040 PROGRAM. 1670 01:06:16,040 --> 01:06:21,840 I'M GOING TO GIVE YOU INSIGHT 1671 01:06:21,840 --> 01:06:25,040 INTO OUR CLINICAL CORRELATIVES 1672 01:06:25,040 --> 01:06:26,160 WE'VE GONE THROUGH. 1673 01:06:26,160 --> 01:06:33,440 FIRST OFF, I WANT TO START BY 1674 01:06:33,440 --> 01:06:34,360 SAYING ANALYZING CORRELATE DATA 1675 01:06:34,360 --> 01:06:35,840 IS A TEAM EFFORT. 1676 01:06:35,840 --> 01:06:37,840 WE USE BLOOD DRAWS, FROM A BLOOD 1677 01:06:37,840 --> 01:06:40,600 DRAW FROM A SINGLE PATIENT WE 1678 01:06:40,600 --> 01:06:42,120 GET CLINICAL SAMPLES. 1679 01:06:42,120 --> 01:06:44,720 THEY GO TO THE CLINICAL CENTER 1680 01:06:44,720 --> 01:06:46,600 LAB MEDICINE FOR ROUTINE 1681 01:06:46,600 --> 01:06:47,040 TESTING. 1682 01:06:47,040 --> 01:06:51,400 AND ALSO GO TO OUR FLOW 1683 01:06:51,400 --> 01:06:53,400 CYTOMETRY DEPARTMENT, IN NCI, 1684 01:06:53,400 --> 01:06:55,720 FOR DISEASE BURDEN AND 1685 01:06:55,720 --> 01:06:56,880 CHARACTERISTICS OF LEUKEMIA AND 1686 01:06:56,880 --> 01:06:59,560 TO TELLING US CAR T CELL 1687 01:06:59,560 --> 01:07:00,240 PERCENTAGE. 1688 01:07:00,240 --> 01:07:01,800 RESEARCH SAMPLES ARE COLLECTED. 1689 01:07:01,800 --> 01:07:06,640 WE GET INFORMATION ON CYTOKINES 1690 01:07:06,640 --> 01:07:07,720 THAT ARE RUN THROUGH NCI 1691 01:07:07,720 --> 01:07:09,040 FREDERICK AND WE HAVE 1692 01:07:09,040 --> 01:07:12,440 INFORMATION ON CAR T CELL 1693 01:07:12,440 --> 01:07:14,960 NUMBERS AND OTHER INFORMATION 1694 01:07:14,960 --> 01:07:19,480 FROM OUR LAB IN THE POB. 1695 01:07:19,480 --> 01:07:21,520 FINDINGS FROM THE COLLECTION OF 1696 01:07:21,520 --> 01:07:23,560 THIS INFORMATION AND DATA THAT'S 1697 01:07:23,560 --> 01:07:25,000 RUN HAVE LED TO MULTIPLE 1698 01:07:25,000 --> 01:07:27,800 PUBLICATIONS YOU CAN SEE FROM 1699 01:07:27,800 --> 01:07:31,880 OUR CD19 CAR, CD22 CAR, LOOKING 1700 01:07:31,880 --> 01:07:35,040 AT EXTRAMEDULLARY DISEASE AND 1701 01:07:35,040 --> 01:07:35,640 NEUROTOXICITY. 1702 01:07:35,640 --> 01:07:38,880 AND YOU CAN SEE WE USE 1703 01:07:38,880 --> 01:07:39,760 INFORMATION FROM STUDYING 1704 01:07:39,760 --> 01:07:41,840 CYTOKINES, FROM LOOKING AT THE 1705 01:07:41,840 --> 01:07:43,600 PERCENTAGE OF CAR, USING 1706 01:07:43,600 --> 01:07:46,320 RADIOLOGY STUDIES TO EVALUATE 1707 01:07:46,320 --> 01:07:48,160 DISEASE BURDEN, AS WELL AS 1708 01:07:48,160 --> 01:07:49,920 FINDINGS FROM LAB MEDICINE, 1709 01:07:49,920 --> 01:07:54,240 LOOKING AT BONE MARROW RESULTS. 1710 01:07:54,240 --> 01:08:00,320 SO WE'RE LOOKING AT THE IMPACT 1711 01:08:00,320 --> 01:08:01,200 OF LYMPHO-DEPLETING CHEMOTHERAPY 1712 01:08:01,200 --> 01:08:03,800 AND OUTCOMES, WORKING WITH THE 1713 01:08:03,800 --> 01:08:05,560 NIH CLINICAL CENTER INFECTIOUS 1714 01:08:05,560 --> 01:08:07,360 DISEASE TEAM TO OPTIMALLY DEFINE 1715 01:08:07,360 --> 01:08:09,560 INFECTION RISKS AND TREAT AND 1716 01:08:09,560 --> 01:08:11,240 PREVENT INFECTION IN RECIPIENTS 1717 01:08:11,240 --> 01:08:12,760 OF CAR T CELLS, COLLABORATING 1718 01:08:12,760 --> 01:08:16,440 WITH THE CENTER FOR CELLULAR 1719 01:08:16,440 --> 01:08:21,120 ENGINEERING AND TAYLOR LAB TO 1720 01:08:21,120 --> 01:08:22,880 FURTHER INTERROGATE PROPERTIES 1721 01:08:22,880 --> 01:08:24,120 CRITICAL TO TOXICITIES AND 1722 01:08:24,120 --> 01:08:25,400 RESPONSE, TRAINING A NEW 1723 01:08:25,400 --> 01:08:28,240 GENERATION OF CAR T CELL 1724 01:08:28,240 --> 01:08:28,520 PROVIDERS. 1725 01:08:28,520 --> 01:08:30,920 [APPLAUSE] 1726 01:08:30,920 --> 01:08:36,920 1727 01:08:36,920 --> 01:08:41,080 1728 01:08:41,080 --> 01:08:42,080 >> I'M NAOMI TAYLOR, SENIOR 1729 01:08:42,080 --> 01:08:45,440 INVESTIGATOR IN THE PEDIATRIC 1730 01:08:45,440 --> 01:08:50,400 ONCOLOGY BRANCH, ARRIVED IN 1731 01:08:50,400 --> 01:08:53,360 2018, HONOR THE LEADING THE LAB 1732 01:08:53,360 --> 01:08:54,680 BASED RESEARCH WORKING WITH 1733 01:08:54,680 --> 01:08:56,720 NIRALI AND TEAM. 1734 01:08:56,720 --> 01:08:58,600 BEFORE STARTING I WANT TO SPEND 1735 01:08:58,600 --> 01:09:01,000 20 SECONDS OF MY THREE MINUTES 1736 01:09:01,000 --> 01:09:02,200 IN THANKING AND GIVING A SHOUT 1737 01:09:02,200 --> 01:09:03,760 OUT TO THE PEOPLE IN THE LAB 1738 01:09:03,760 --> 01:09:06,560 BECAUSE EVERYTHING THAT YOU SEE 1739 01:09:06,560 --> 01:09:09,760 HERE TODAY, THE PATIENTS BEING 1740 01:09:09,760 --> 01:09:11,080 TREATED BY THERAPIES, THAT 1741 01:09:11,080 --> 01:09:12,920 REPRESENTS HOURS AND HOURS AND 1742 01:09:12,920 --> 01:09:15,000 HOURS OF WORK AND DAYS AND 1743 01:09:15,000 --> 01:09:15,760 MONTHS AND YEARS. 1744 01:09:15,760 --> 01:09:17,200 NONE OF THE TREATMENTS THAT ANY 1745 01:09:17,200 --> 01:09:19,840 OF THE PATIENTS HAVE GOTTEN HAVE 1746 01:09:19,840 --> 01:09:20,240 HAPPENED OVERNIGHT. 1747 01:09:20,240 --> 01:09:22,400 I THINK IT'S ALWAYS A MIRACLE 1748 01:09:22,400 --> 01:09:23,520 WHEN THESE TREATMENTS WORK. 1749 01:09:23,520 --> 01:09:26,400 IT'S ALWAYS WHAT WE LOOK FOR, 1750 01:09:26,400 --> 01:09:29,120 NIRALI WILL TELL YOU IT DOESN'T 1751 01:09:29,120 --> 01:09:30,720 MATTER WHAT THE MOUTH SAYS, WE 1752 01:09:30,720 --> 01:09:33,280 NEED TO SEE WHAT THE PATIENT 1753 01:09:33,280 --> 01:09:33,920 SAYS. 1754 01:09:33,920 --> 01:09:35,120 WE SPEND HUGE AMOUNTS OF EFFORT 1755 01:09:35,120 --> 01:09:37,000 BEFORE GETTING TO THE POINT OF 1756 01:09:37,000 --> 01:09:38,360 TREATING A PATIENT. 1757 01:09:38,360 --> 01:09:39,840 BEFORE STARTING, I WANT TO -- I 1758 01:09:39,840 --> 01:09:42,560 SEE SOME PEOPLE IN THE LAB HERE. 1759 01:09:42,560 --> 01:09:50,360 I WANT TO GIVE A SHOUT OUT TO 1760 01:09:50,360 --> 01:09:51,440 THE TRAINEES, STUDENTS, 1761 01:09:51,440 --> 01:09:52,520 POSTDOCS, STAFFER BIOLOGISTS, 1762 01:09:52,520 --> 01:09:53,640 HERE DAY AND NIGHT. 1763 01:09:53,640 --> 01:09:55,920 FOR THOSE NOT INVOLVED IN THE 1764 01:09:55,920 --> 01:09:57,720 LAB, IT'S OFTEN THAT MORE 1765 01:09:57,720 --> 01:09:59,200 EXPERIMENTS FAIL THAN WORK. 1766 01:09:59,200 --> 01:10:00,960 AND SO I'M LOOKING AT SOME 1767 01:10:00,960 --> 01:10:02,080 PATIENTS AND THEIR FAMILIES TO 1768 01:10:02,080 --> 01:10:04,040 SAY THIS REQUIRES A HUGE AMOUNT 1769 01:10:04,040 --> 01:10:06,000 OF WORK, HUGE AMOUNT OF EFFORT, 1770 01:10:06,000 --> 01:10:07,320 AND SO BEFORE STARTING I WANT TO 1771 01:10:07,320 --> 01:10:08,960 GIVE A SHOUT OUT TO THE HEROES 1772 01:10:08,960 --> 01:10:11,040 IN THE LAB. 1773 01:10:11,040 --> 01:10:12,760 IT'S BECAUSE OF THEM WE MOVE 1774 01:10:12,760 --> 01:10:15,360 FORWARD WITH TREATMENTS TO THE 1775 01:10:15,360 --> 01:10:16,280 PATIENTS AND THEIR FAMILIES. 1776 01:10:16,280 --> 01:10:19,000 I THOUGHT I WOULD GIVE AN 1777 01:10:19,000 --> 01:10:21,680 EXAMPLE OF THREE AREAS IN TERMS 1778 01:10:21,680 --> 01:10:23,440 OF BIOLOGICAL CORRELATES THAT WE 1779 01:10:23,440 --> 01:10:26,680 NEED TO LOOK AT IN ORDER TO MOVE 1780 01:10:26,680 --> 01:10:28,280 FORWARD TO DO A BETTER JOB. 1781 01:10:28,280 --> 01:10:30,440 DOES THE POINTER WORK? 1782 01:10:30,440 --> 01:10:30,760 YEAH. 1783 01:10:30,760 --> 01:10:31,920 THREE EXAMPLES. 1784 01:10:31,920 --> 01:10:34,040 WE'RE DOING MORE. 1785 01:10:34,040 --> 01:10:36,000 THOSE WHO KNOW ME KNOW I DO LOTS 1786 01:10:36,000 --> 01:10:37,000 OF DIFFERENT THINGS, PEOPLE IN 1787 01:10:37,000 --> 01:10:40,360 THE LAB ARE GOOD AT THIS. 1788 01:10:40,360 --> 01:10:42,560 WITH THE CCE, WITH DAVID AND 1789 01:10:42,560 --> 01:10:44,760 STEVE, IT'S NOT CLEAR AS TO WHAT 1790 01:10:44,760 --> 01:10:46,440 MANUFACTURING PRACTICES ARE THE 1791 01:10:46,440 --> 01:10:48,160 BEST FOR MAKING CAR T CELLS. 1792 01:10:48,160 --> 01:10:50,000 YOU HEARD FROM DAVID THAT WE'RE 1793 01:10:50,000 --> 01:10:51,880 VERY GOOD AT MAKING CAR T CELLS 1794 01:10:51,880 --> 01:10:54,280 BUT BEST IS ALWAYS A WORD THAT'S 1795 01:10:54,280 --> 01:10:55,160 DIFFICULT TO UNDERSTAND. 1796 01:10:55,160 --> 01:10:58,640 WE NEED TO HAVE A MUCH BETTER 1797 01:10:58,640 --> 01:11:00,440 IDEA OF THE TOXICITIES COMING 1798 01:11:00,440 --> 01:11:02,600 FROM CAR T CELLS, AND ALSO WE 1799 01:11:02,600 --> 01:11:04,240 NEED TO FIGURE OUT AGAIN I'M 1800 01:11:04,240 --> 01:11:06,480 GOING TO USE THE WORD IN 1801 01:11:06,480 --> 01:11:08,600 QUOTATIONS, WHAT IS THE BEST? 1802 01:11:08,600 --> 01:11:10,640 IF A PATIENT FAILED A CD19 CAR T 1803 01:11:10,640 --> 01:11:12,240 CELL TRIAL WHAT IS THE BEST WAY 1804 01:11:12,240 --> 01:11:13,520 TO BRING THEM FORWARD AND WHAT 1805 01:11:13,520 --> 01:11:14,880 ARE THE TRIALS WE WANT TO MAKE 1806 01:11:14,880 --> 01:11:16,360 SURE THEY CAN GO ON THAT WOULD 1807 01:11:16,360 --> 01:11:18,240 GIVE THEM THE BEST CHANCE OF 1808 01:11:18,240 --> 01:11:20,200 SUCCEEDING IN A SECOND ONE? 1809 01:11:20,200 --> 01:11:22,080 JUST TO GIVE AN EXAMPLE, I'LL 1810 01:11:22,080 --> 01:11:24,480 SHOW SOME OF THE WORK ON THIS, 1811 01:11:24,480 --> 01:11:26,800 I'M GETTING AHEAD OF MYSELF, IS 1812 01:11:26,800 --> 01:11:29,080 THAT IN THE LAB PATIENTS ARE 1813 01:11:29,080 --> 01:11:31,160 BEING TREATED, FOR EXAMPLE, IN 1814 01:11:31,160 --> 01:11:33,440 THE NIH, IN STANFORD, DIFFERENT 1815 01:11:33,440 --> 01:11:34,480 CENTERS BY VERY DIFFERENT 1816 01:11:34,480 --> 01:11:37,960 METHODS OF MAKING CAR T CELLS 1817 01:11:37,960 --> 01:11:39,960 WITH DIFFERENT CYTOKINE SUPPORT 1818 01:11:39,960 --> 01:11:41,880 AND DIFFERENT WAYS OF SELECTING. 1819 01:11:41,880 --> 01:11:43,120 YOU HEARD ABOUT CYTOKINE RELEASE 1820 01:11:43,120 --> 01:11:46,080 SYNDROME BUT ONE OF THE THINGS 1821 01:11:46,080 --> 01:11:47,920 NIRALI AND GROUP HAVE DONE IS TO 1822 01:11:47,920 --> 01:11:53,360 SEE THERE'S A SECONDARY PEAK OF 1823 01:11:53,360 --> 01:11:54,160 CYTOKINES, INFLAMMATORY 1824 01:11:54,160 --> 01:11:58,640 RESPONSE, VERY SIMILAR TO HLH, 1825 01:11:58,640 --> 01:12:00,600 WE STILL DON'T UNDERSTAND WHY 1826 01:12:00,600 --> 01:12:01,720 THIS OCCURS. 1827 01:12:01,720 --> 01:12:03,360 AGAIN, AS I MENTIONED, IF WE 1828 01:12:03,360 --> 01:12:06,280 HAVE A PATIENT WHO FAILED A CD19 1829 01:12:06,280 --> 01:12:08,440 CAR T CELL TRIAL OR CD22, WHAT 1830 01:12:08,440 --> 01:12:10,760 DO WE WANT TO DO NEXT? 1831 01:12:10,760 --> 01:12:13,200 HOW DO WE WANT TO TREAT PATIENTS 1832 01:12:13,200 --> 01:12:14,720 WHO ARE ACTUALLY HAVING AMLs, 1833 01:12:14,720 --> 01:12:17,360 NOT JUST A.L.L.s, AND OTHER 1834 01:12:17,360 --> 01:12:17,640 LEUKEMIAS? 1835 01:12:17,640 --> 01:12:19,640 TO GIVE A WAY OF WHAT WE'RE 1836 01:12:19,640 --> 01:12:20,840 LOOKING AT THIS, INFORMATION 1837 01:12:20,840 --> 01:12:22,720 WHICH I DON'T EXPECT YOU TO LOOK 1838 01:12:22,720 --> 01:12:24,320 AT IN DETAIL, OR NEITHER TO 1839 01:12:24,320 --> 01:12:25,680 UNDERSTAND, BUT JUST TO SAY IF 1840 01:12:25,680 --> 01:12:28,080 WE LOOK AT DIFFERENT SUBSETS 1841 01:12:28,080 --> 01:12:29,600 MAKING T CELLS IN DIFFERENT 1842 01:12:29,600 --> 01:12:34,280 WAYS, THIS IS COMING FROM THE 1843 01:12:34,280 --> 01:12:37,080 CCE, CLINICALLY RELEVANT CAR T 1844 01:12:37,080 --> 01:12:40,040 CELLS, WE HAVE DIFFERENT T CELL 1845 01:12:40,040 --> 01:12:40,840 SUBSETS WITH PERCENTAGES, IF 1846 01:12:40,840 --> 01:12:44,480 CELLS ARE MADE IN A BAG OR 1847 01:12:44,480 --> 01:12:44,840 PRODIGY. 1848 01:12:44,840 --> 01:12:46,720 WHAT DOES THAT MEAN IN TERMS OF 1849 01:12:46,720 --> 01:12:48,760 OPTIMAL THINGS GOING FORWARD. 1850 01:12:48,760 --> 01:12:50,080 WE'RE NOT SURE. 1851 01:12:50,080 --> 01:12:52,280 WE NEED TO DEFINE DIFFERENCES. 1852 01:12:52,280 --> 01:12:54,920 WE NEED TO FIGURE OUT WHAT ARE 1853 01:12:54,920 --> 01:12:57,560 DIFFERENCES BETWEEN A PATIENT, 1854 01:12:57,560 --> 01:12:59,720 SORRY, BETWEEN A PATIENT WHO 1855 01:12:59,720 --> 01:13:02,240 GETS THE SECONDARY INFLAMMATORY 1856 01:13:02,240 --> 01:13:08,280 RESPONSE AND THOSE WHO DON'T. 1857 01:13:08,280 --> 01:13:10,160 YOU CAN SEE WE'RE STARTING -- 1858 01:13:10,160 --> 01:13:12,760 OKAY, I'LL STOP TRYING TO POINT. 1859 01:13:12,760 --> 01:13:14,280 IN THE MIDDLE PANEL, WE'RE 1860 01:13:14,280 --> 01:13:15,480 STARTING TO HAVE DIFFERENCES IN 1861 01:13:15,480 --> 01:13:17,880 TERMS OF CYTOKINE PROFILES OF 1862 01:13:17,880 --> 01:13:18,560 PATIENTS WHO HAVE LATE 1863 01:13:18,560 --> 01:13:19,760 TOXICITIES AND THOSE WHO DON'T. 1864 01:13:19,760 --> 01:13:21,680 IF YOU CAN SEE AT THE BOTTOM 1865 01:13:21,680 --> 01:13:27,040 HERE WE CAN START TO USE 1866 01:13:27,040 --> 01:13:27,800 HIGH-THROUGHPUT ROBOTICS TO SEE 1867 01:13:27,800 --> 01:13:31,520 HOW THEY ARE GOING TO RESPOND IN 1868 01:13:31,520 --> 01:13:34,240 TERMS OF CYTOKINES WHEN GETTING 1869 01:13:34,240 --> 01:13:34,760 DIFFERENT CARs. 1870 01:13:34,760 --> 01:13:39,600 THE BLUE LINE IS THE CAR WE'VE 1871 01:13:39,600 --> 01:13:41,600 MOVE FORWARD WITH IN TERMS OF 1872 01:13:41,600 --> 01:13:42,240 CLINICAL TRIALS. 1873 01:13:42,240 --> 01:13:45,480 THERE'S STILL A HUGE AMOUNT TO 1874 01:13:45,480 --> 01:13:45,640 DO. 1875 01:13:45,640 --> 01:13:49,560 WE HAVE NEW CLINICAL TRIALS WITH 1876 01:13:49,560 --> 01:13:52,480 THE CD19-22 BY VALENT, CD33 FOR 1877 01:13:52,480 --> 01:13:55,800 AML, NEED TO IMPROVE THOSE, 1878 01:13:55,800 --> 01:14:00,360 UPCOMING TRIALS WITH THE BLUE 1879 01:14:00,360 --> 01:14:02,000 LINE, NEW TARGETS, WORKING ON 1880 01:14:02,000 --> 01:14:03,880 TRYING TO MAKE NEW CAR DESIGNS 1881 01:14:03,880 --> 01:14:05,560 AND TO USE NEW TECHNOLOGIES TO 1882 01:14:05,560 --> 01:14:10,360 TRY TO FIGURE OUT HOW TO 1883 01:14:10,360 --> 01:14:11,440 OPTIMIZE EFFICACY AND REDUCE 1884 01:14:11,440 --> 01:14:12,640 TOXICITY IN CLINICAL TRIALS AND 1885 01:14:12,640 --> 01:14:14,400 TO TRY TO UNDERSTAND HOW IN THE 1886 01:14:14,400 --> 01:14:19,240 CONTEXT OF PATIENTS WHO HAVE 1887 01:14:19,240 --> 01:14:20,640 DIFFERENT METABOLISMS, HOW WE 1888 01:14:20,640 --> 01:14:22,880 CAN MAKE CARs WORK BETTER. 1889 01:14:22,880 --> 01:14:24,160 I'LL END THERE AND THANK YOU 1890 01:14:24,160 --> 01:14:24,600 AGAIN. 1891 01:14:24,600 --> 01:14:25,680 I'LL FINISH BY THANKING ALL THE 1892 01:14:25,680 --> 01:14:26,800 PEOPLE IN THE LAB BECAUSE NONE 1893 01:14:26,800 --> 01:14:28,080 OF THIS COULD HAVE HAPPENED 1894 01:14:28,080 --> 01:14:29,120 WITHOUT THEM. 1895 01:14:29,120 --> 01:14:29,800 SO THANK YOU. 1896 01:14:29,800 --> 01:14:32,640 [APPLAUSE] 1897 01:14:32,640 --> 01:14:38,880 1898 01:14:38,880 --> 01:14:41,280 1899 01:14:41,280 --> 01:14:42,560 >> I'M CONSTANCE FROM FLOW 1900 01:14:42,560 --> 01:14:42,840 CYTOMETRY. 1901 01:14:42,840 --> 01:14:45,400 THANK YOU FOR BEING HERE TODAY 1902 01:14:45,400 --> 01:14:47,640 TO LISTEN. 1903 01:14:47,640 --> 01:14:53,800 1904 01:14:53,800 --> 01:14:54,560 IT'S CLEAR IT'S WONDERFUL WHEN 1905 01:14:54,560 --> 01:14:56,480 CAR T CELLS WORK BUT WHAT DO YOU 1906 01:14:56,480 --> 01:14:57,520 DO WHEN THEY DON'T? 1907 01:14:57,520 --> 01:14:59,600 IT'S CLEAR TO US THAT IT'S 1908 01:14:59,600 --> 01:15:02,120 IMPORTANT TO UNDERSTAND AND ASK 1909 01:15:02,120 --> 01:15:04,320 QUESTIONS ABOUT WHY RESISTANCE 1910 01:15:04,320 --> 01:15:04,520 OCCURS. 1911 01:15:04,520 --> 01:15:07,080 COULD THIS BE DUE BECAUSE OF A 1912 01:15:07,080 --> 01:15:11,760 FUNCTION OF THE CAR T CELLS, DUE 1913 01:15:11,760 --> 01:15:14,480 DO A MECHANISM TO AVOID THERAPY? 1914 01:15:14,480 --> 01:15:16,000 OR SOME ROLE THE 1915 01:15:16,000 --> 01:15:17,360 MICROENVIRONMENT THAT 1916 01:15:17,360 --> 01:15:19,000 CONTRIBUTES TO RESISTANCE? 1917 01:15:19,000 --> 01:15:20,720 WE'RE HAPPY TO SAY FLOW 1918 01:15:20,720 --> 01:15:23,880 CYTOMETRY CAN HELP ANSWER SOME 1919 01:15:23,880 --> 01:15:24,680 QUESTIONS, OFTER MULTIPLEX 1920 01:15:24,680 --> 01:15:27,840 PHENOTYPING OF MULTIPLE CELL 1921 01:15:27,840 --> 01:15:29,400 POPULATIONS FROM SINGLE SAMPLE, 1922 01:15:29,400 --> 01:15:32,680 WITH HIGH SENSITIVITY. 1923 01:15:32,680 --> 01:15:34,760 WE KNOW FLOW CYTOMETRY 1924 01:15:34,760 --> 01:15:36,960 IDENTIFYING CELL POPULATIONS OF 1925 01:15:36,960 --> 01:15:39,280 INTEREST, AND THIS CAN BE 1926 01:15:39,280 --> 01:15:41,120 EFFECTIVE BRIDGE TO OTHER 1927 01:15:41,120 --> 01:15:44,640 MODALITIES TO FURTHER ANSWER 1928 01:15:44,640 --> 01:15:46,560 THESE QUESTIONS. 1929 01:15:46,560 --> 01:15:52,600 FOR THE LAST TEN YEARS, FLOW 1930 01:15:52,600 --> 01:15:54,600 CYTOMETRY HAS MONITORED 1931 01:15:54,600 --> 01:15:56,000 EXPANSION, MOST IMPORTANTLY 1932 01:15:56,000 --> 01:15:57,560 EXAMINED RELATIONSHIP TO DISEASE 1933 01:15:57,560 --> 01:15:57,800 STATUS. 1934 01:15:57,800 --> 01:15:59,760 YOU CAN SEE IN THE FIGURE IN THE 1935 01:15:59,760 --> 01:16:02,400 LOWER RIGHT CORNER FOR THIS 1936 01:16:02,400 --> 01:16:04,480 PARTICULAR PATIENT THAT HAD 1937 01:16:04,480 --> 01:16:06,440 LEUKEMIA IN RED, THE DISEASE 1938 01:16:06,440 --> 01:16:08,200 DISAPPEARED AT THE SAME TIME 1939 01:16:08,200 --> 01:16:10,960 THERE'S AN EXPANSION OF CD19 CAR 1940 01:16:10,960 --> 01:16:12,240 T CELLS IN BLUE. 1941 01:16:12,240 --> 01:16:13,520 SUBSEQUENTLY THERE'S A RECOVERY 1942 01:16:13,520 --> 01:16:15,480 OF NORMAL B CELLS SHOWN IN 1943 01:16:15,480 --> 01:16:15,840 GREEN. 1944 01:16:15,840 --> 01:16:19,000 THIS WAS FROM THE PAPER 1945 01:16:19,000 --> 01:16:21,400 PUBLISHED IN 2015 FROM LEE ET 1946 01:16:21,400 --> 01:16:21,880 AL. 1947 01:16:21,880 --> 01:16:24,920 WE'VE OBSERVED A VERY NOTABLE 1948 01:16:24,920 --> 01:16:28,600 RAPID EARLY RECOVERY OF NORMAL 1949 01:16:28,600 --> 01:16:29,800 CIRCULATING TRANSITIONAL B 1950 01:16:29,800 --> 01:16:31,840 CELLS, THIS CAN SOMETIMES HAPPEN 1951 01:16:31,840 --> 01:16:34,640 AFTER OTHER TIMES OF TRADITIONAL 1952 01:16:34,640 --> 01:16:34,880 THERAPY. 1953 01:16:34,880 --> 01:16:36,520 BUT WITH CD19 CAR T CELL THERAPY 1954 01:16:36,520 --> 01:16:38,680 IT HAPPENS IN TERMS OF WEEKS, 1955 01:16:38,680 --> 01:16:43,440 EVEN DAYS AFTER THERAPY IS 1956 01:16:43,440 --> 01:16:43,760 RECEIVED. 1957 01:16:43,760 --> 01:16:46,320 THE LABORATORY HAS BEEN ABLE TO 1958 01:16:46,320 --> 01:16:47,600 IMPLEMENT ALTERNATIVE FLOW 1959 01:16:47,600 --> 01:16:49,440 CYTOMETRY STRATEGY TO IDENTIFY 1960 01:16:49,440 --> 01:16:54,520 DISEASE, THIS HAD TO BE DONE FOR 1961 01:16:54,520 --> 01:16:56,160 DETECTION OF CD19 NEGATIVE 1962 01:16:56,160 --> 01:16:57,200 DISEASE, WHEN IT DISAPPEARS FROM 1963 01:16:57,200 --> 01:16:59,000 THE SURFACE OF THE CELL. 1964 01:16:59,000 --> 01:17:00,560 WITHOUT THIS STRATEGY IN PLACE 1965 01:17:00,560 --> 01:17:05,960 YOU CAN ENTIRELY MISS DETECTING 1966 01:17:05,960 --> 01:17:06,480 RESIDUAL DISEASE. 1967 01:17:06,480 --> 01:17:09,200 WE'RE ABLE TO PROVIDE 1968 01:17:09,200 --> 01:17:09,840 INFORMATION ON ANTIGEN 1969 01:17:09,840 --> 01:17:10,920 QUANTITATION, WHICH TELLS NUMBER 1970 01:17:10,920 --> 01:17:12,120 OF MOLECULES ON THE SURFACE OF 1971 01:17:12,120 --> 01:17:14,240 THE CELL THAT YOU'RE INTERESTED 1972 01:17:14,240 --> 01:17:15,080 IN LOOKING AT. 1973 01:17:15,080 --> 01:17:16,400 THIS HAS BEEN HELPFUL BECAUSE 1974 01:17:16,400 --> 01:17:18,480 IT'S ALLOWED US TO UNDERSTAND 1975 01:17:18,480 --> 01:17:20,520 BETTER THE RELATIONSHIP TO 1976 01:17:20,520 --> 01:17:22,960 RESPONSE TO THERAPY, ALSO 1977 01:17:22,960 --> 01:17:23,880 ALLOWED MODULATION OF THE 1978 01:17:23,880 --> 01:17:26,920 TARGETED ANTIGEN TO COME APART 1979 01:17:26,920 --> 01:17:28,800 IN THE THERAPEUTIC STRATEGY AS 1980 01:17:28,800 --> 01:17:29,880 SHOWN IN 2019. 1981 01:17:29,880 --> 01:17:32,080 OUR ABILITY TO PROVIDE THIS TYPE 1982 01:17:32,080 --> 01:17:38,200 OF TESTING IN PLACES OUTSIDE OF 1983 01:17:38,200 --> 01:17:41,240 BLOOD AND BONE MARROW HAS 1984 01:17:41,240 --> 01:17:44,080 PROVIDED INSIGHT INTO BIOLOGY OF 1985 01:17:44,080 --> 01:17:47,360 EXTRAMEDULLARY DISEASE RELAPSE 1986 01:17:47,360 --> 01:17:48,040 SHOWN IN 2021. 1987 01:17:48,040 --> 01:17:51,480 SO FOR THE FUTURE WHAT DO WE 1988 01:17:51,480 --> 01:17:51,920 SEE? 1989 01:17:51,920 --> 01:17:53,640 WE FORESEE DEVELOPMENT OF 1990 01:17:53,640 --> 01:17:54,720 DIAGNOSTIC APPROACHES AND 1991 01:17:54,720 --> 01:17:59,240 CONTINUING TO TRY TO IMPROVE 1992 01:17:59,240 --> 01:18:00,440 RESIDUAL DISEASE DETECTION 1993 01:18:00,440 --> 01:18:02,360 ESPECIALLY IN ANTIGEN 1994 01:18:02,360 --> 01:18:04,040 REGULATION, LOSS, LINEAGE 1995 01:18:04,040 --> 01:18:04,400 SWITCH. 1996 01:18:04,400 --> 01:18:06,200 WE SEE CONTINUED DEVELOPMENT OF 1997 01:18:06,200 --> 01:18:12,920 ADDITIONAL CAR T CELL DETECTION 1998 01:18:12,920 --> 01:18:14,560 ASSAYS, AND EXPLORE 1999 01:18:14,560 --> 01:18:15,240 COLLABORATIVE RESEARCH, MEASURE 2000 01:18:15,240 --> 01:18:16,960 SUITED TO THE RESEARCH CORE 2001 01:18:16,960 --> 01:18:22,280 FACILITY UNDERWAY WITHIN THE 2002 01:18:22,280 --> 01:18:24,000 LABORATORY PATHOLOGY. 2003 01:18:24,000 --> 01:18:26,400 WE HOPE TO BRING COMPONENTS OF 2004 01:18:26,400 --> 01:18:28,440 THIS COLLABORATIVE RESEARCH TO 2005 01:18:28,440 --> 01:18:30,320 BE APPLIED TO CLINICAL FLOW 2006 01:18:30,320 --> 01:18:31,040 CYTOMETRY TESTING AND HOPEFULLY 2007 01:18:31,040 --> 01:18:32,640 IMPROVE THE LIVES OF THE 2008 01:18:32,640 --> 01:18:33,320 PATIENTS WE SERVE. 2009 01:18:33,320 --> 01:18:34,800 THANK YOU VERY, VERY MUCH. 2010 01:18:34,800 --> 01:18:37,120 [APPLAUSE] 2011 01:18:37,120 --> 01:18:40,640 2012 01:18:40,640 --> 01:18:50,680 2013 01:18:53,440 --> 01:18:54,600 >> HI. 2014 01:18:54,600 --> 01:18:55,640 THANK YOU. 2015 01:18:55,640 --> 01:18:59,120 I'M ROSIE KAPLAN, HAPPY TO BE 2016 01:18:59,120 --> 01:19:01,680 HERE TODAY, BOTH BEING IN THE 2017 01:19:01,680 --> 01:19:04,280 POB AND PART OF THIS TEN YEARS 2018 01:19:04,280 --> 01:19:05,800 THAT HAVE BEEN SO AMAZING. 2019 01:19:05,800 --> 01:19:08,120 NOW TO HAVE THE OPPORTUNITY TO 2020 01:19:08,120 --> 01:19:10,280 TALK TO YOU TODAY ABOUT 2021 01:19:10,280 --> 01:19:11,360 PEDIATRIC ONCOLOGY BRANCH'S 2022 01:19:11,360 --> 01:19:13,680 EFFORTS WITH CAR T CELLS AND 2023 01:19:13,680 --> 01:19:14,440 SOLID TUMORS. 2024 01:19:14,440 --> 01:19:15,880 AND WHAT I'M GOING TO SPEAK 2025 01:19:15,880 --> 01:19:17,520 ABOUT IS A BIGGER GROUP. 2026 01:19:17,520 --> 01:19:18,720 I REPRESENT STANDING UP HERE BUT 2027 01:19:18,720 --> 01:19:20,920 HOPEFULLY YOU SEE ALL THE PEOPLE 2028 01:19:20,920 --> 01:19:22,080 INVOLVED IN THIS EFFORT THAT ARE 2029 01:19:22,080 --> 01:19:23,440 PART OF IT. 2030 01:19:23,440 --> 01:19:25,920 AND CAR T CELL THERAPIES HAVE 2031 01:19:25,920 --> 01:19:28,480 BEEN TRADITIONALLY USED IN 2032 01:19:28,480 --> 01:19:30,880 LEUKEMIAS AND LYMPHOMAS. 2033 01:19:30,880 --> 01:19:35,080 BUT UNLIKE LIQUID SUPERVISORS, 2034 01:19:35,080 --> 01:19:37,000 SOLID TUMORS HAVE UNIQUE 2035 01:19:37,000 --> 01:19:38,200 CHALLENGES. 2036 01:19:38,200 --> 01:19:39,280 AND MOST OF THESE CHALLENGES, 2037 01:19:39,280 --> 01:19:41,280 THIS IS ALL SORT OF THE 2038 01:19:41,280 --> 01:19:42,680 BEGINNING OF THIS JOURNEY FOR 2039 01:19:42,680 --> 01:19:44,000 CAR T CELLS, I BELIEVE. 2040 01:19:44,000 --> 01:19:46,760 A LOT HAVE TO DO WITH TUMOR 2041 01:19:46,760 --> 01:19:48,520 HETEROGENEITY WHICH ALSO EXISTS 2042 01:19:48,520 --> 01:19:51,040 IN LIQUID TUMORS, BUT IS EVEN 2043 01:19:51,040 --> 01:19:52,640 MAYBE MORE PRONOUNCED IN SOLID 2044 01:19:52,640 --> 01:19:55,160 TUMORS IN TERMS OF EXPRESSION OF 2045 01:19:55,160 --> 01:19:57,280 TARGETS AND THE MULTITUDE OF 2046 01:19:57,280 --> 01:19:59,440 TUMOR ANTIGENS AND TARGETS THAT 2047 01:19:59,440 --> 01:20:00,960 COULD BE EXAMINED. 2048 01:20:00,960 --> 01:20:02,080 OF COURSE, AN AREA THAT'S NEAR 2049 01:20:02,080 --> 01:20:04,560 AND DEAR TO MY HEART IS 2050 01:20:04,560 --> 01:20:07,560 COMPLEXITY OF TUMOR AND 2051 01:20:07,560 --> 01:20:09,080 METASTATIC MICROENVIRONMENTS, 2052 01:20:09,080 --> 01:20:10,640 PATIENTS CAN HAVE LOCALIZED AND 2053 01:20:10,640 --> 01:20:12,720 SYSTEMIC TUMORS AT THE TIME, MAY 2054 01:20:12,720 --> 01:20:14,440 BE BOTH DIFFERENT TUMOR BIOLOGY 2055 01:20:14,440 --> 01:20:15,600 AND MICROENVIRONMENT. 2056 01:20:15,600 --> 01:20:18,040 AND THE CAR T CELLS THEMSELVES 2057 01:20:18,040 --> 01:20:20,160 HAVE UNIQUE CHALLENGES AND SOLID 2058 01:20:20,160 --> 01:20:24,080 TUMORS RELATED TO LIMITED 2059 01:20:24,080 --> 01:20:25,200 PERSISTENCE, EXHAUSTION, 2060 01:20:25,200 --> 01:20:28,040 POTENTIALLY IMPAIRED MEMORY, AS 2061 01:20:28,040 --> 01:20:29,440 WELL AS PRESENTATION AND DYNAMIC 2062 01:20:29,440 --> 01:20:30,000 ISSUES. 2063 01:20:30,000 --> 01:20:32,720 YOU CAN SEE THAT IN THE IMAGE 2064 01:20:32,720 --> 01:20:34,360 I'M SHOWING, REPRESENTING THE 2065 01:20:34,360 --> 01:20:37,760 DENSITY OF TUMOR WHEN YOU HAVE A 2066 01:20:37,760 --> 01:20:40,600 SOLID TUMOR AND THE REAL 2067 01:20:40,600 --> 01:20:44,560 COMPLEXITIES OF THE UNIQUE AREAS 2068 01:20:44,560 --> 01:20:46,320 WITHIN THAT, AND MULTIPLE CELLS 2069 01:20:46,320 --> 01:20:47,960 THAT WORK IN CONCERT WITH THE 2070 01:20:47,960 --> 01:20:50,800 TUMOR AND ARE INVOLVED IN THIS 2071 01:20:50,800 --> 01:20:51,000 PROCESS. 2072 01:20:51,000 --> 01:20:53,760 AND ONE OF THE BIGGEST AND FIRST 2073 01:20:53,760 --> 01:20:57,120 EFFORTS THAT WERE STARTED IN 2074 01:20:57,120 --> 01:20:59,320 CRYSTAL MAKEL'S LAB WHEN SHE WAS 2075 01:20:59,320 --> 01:21:04,880 HERE WAS EXPLORING A TARGET 2076 01:21:04,880 --> 01:21:11,040 THAT'S A MOIETY KNOWN AS GD2, A 2077 01:21:11,040 --> 01:21:14,440 KNOWN TARGET IN NEUROBLASTOMA 2078 01:21:14,440 --> 01:21:18,680 AND OSTEOSARCOMA, CRYSTAL'S 2079 01:21:18,680 --> 01:21:20,640 GROUP WITH THE HELP OF MICHAEL 2080 01:21:20,640 --> 01:21:22,400 AND OTHERS STARTED A PHASE 1 2081 01:21:22,400 --> 01:21:26,360 TRIAL OF T CELLS, ANTI-GD2 2082 01:21:26,360 --> 01:21:29,600 CHIMERIC ANTIGEN RECEPTORS IN 2083 01:21:29,600 --> 01:21:31,040 PATIENTS SOLID TUMORS, NOT ONLY 2084 01:21:31,040 --> 01:21:33,320 ABLE TO REALLY DO ROBUST 2085 01:21:33,320 --> 01:21:35,840 PHENOTYPING OF SOLID TUMORS TO 2086 01:21:35,840 --> 01:21:40,360 DETERMINE THAT OSTEOSARCOMA 2087 01:21:40,360 --> 01:21:41,440 INDEED WAS HIGHLY EXPRESSING BUT 2088 01:21:41,440 --> 01:21:47,120 ABLE WITH THE HELP OF THE ENTIRE 2089 01:21:47,120 --> 01:21:50,520 TEAM IN CCE TO MANUFACTURE THIS 2090 01:21:50,520 --> 01:21:52,040 CAR CELL PRODUCT AND EXCITINGLY 2091 01:21:52,040 --> 01:21:54,680 WERE ABLE TO SHOW IT WAS QUITE 2092 01:21:54,680 --> 01:21:59,160 SAFE AND THAT CONCERNS OF 2093 01:21:59,160 --> 01:22:00,800 ON-TARGET OFF-TUMOR NEUROPATHIC 2094 01:22:00,800 --> 01:22:04,640 EFFECTS WITH THE ANTIBODY WERE 2095 01:22:04,640 --> 01:22:06,520 NOT SEEN WITH THE CAR, EACH 2096 01:22:06,520 --> 01:22:07,840 THERAPY IS UNIQUE THAT WAY AND 2097 01:22:07,840 --> 01:22:13,440 IT WAS THE FIRST TRIAL TO ENROLL 2098 01:22:13,440 --> 01:22:14,960 OSTEOSARCOMA PATIENTS. 2099 01:22:14,960 --> 01:22:17,280 THE MOST EXCITING PART FOR THIS, 2100 01:22:17,280 --> 01:22:19,760 IT'S BEEN A TREMENDOUS 2101 01:22:19,760 --> 01:22:20,880 OPPORTUNITY TO LEARN FROM OUR 2102 01:22:20,880 --> 01:22:23,160 CLINICAL TRIAL AND TAKE THIS 2103 01:22:23,160 --> 01:22:24,600 CORRELATEIVE STUDY. 2104 01:22:24,600 --> 01:22:26,160 WE FOUND WE COULD SEE EXPANSION 2105 01:22:26,160 --> 01:22:29,600 IN PATIENTS TO THE LEVEL IN 19 2106 01:22:29,600 --> 01:22:32,160 CAR, EXCITING IN LIQUID TUMOR, 2107 01:22:32,160 --> 01:22:34,000 GREAT VARIABILITY, WE'RE ABLE TO 2108 01:22:34,000 --> 01:22:37,640 SPLIT PATIENTS INTO ONES THAT 2109 01:22:37,640 --> 01:22:39,160 EXPAND AND ONES THAT DIDN'T. 2110 01:22:39,160 --> 01:22:41,760 IT WAS DISAPPOINTING WE DIDN'T 2111 01:22:41,760 --> 01:22:43,880 SEE RESPONSES, WERE WORRIED THAT 2112 01:22:43,880 --> 01:22:46,840 WAS MAYBE RELATED TO FINDINGS IN 2113 01:22:46,840 --> 01:22:50,560 THE LAB, AND JUST AS NAOMI 2114 01:22:50,560 --> 01:22:52,000 TAYLOR WAS SAYING, WE HAD TO GO 2115 01:22:52,000 --> 01:22:53,160 BACK TO THE LAB AND UNDERSTAND 2116 01:22:53,160 --> 01:22:53,840 WHY. 2117 01:22:53,840 --> 01:22:56,120 ONE OF THE THINGS DR. MAKEL'S 2118 01:22:56,120 --> 01:22:59,600 GROUP FOUND WAS T CELLS WERE 2119 01:22:59,600 --> 01:23:00,760 GETTING EXHAUSTED IN THE MAKING 2120 01:23:00,760 --> 01:23:02,280 OF THEM BEFORE THEY GOT INTO THE 2121 01:23:02,280 --> 01:23:03,920 PATIENT AND THAT GOES BACK TO 2122 01:23:03,920 --> 01:23:05,120 THE DIFFERENCES IN MANUFACTURING 2123 01:23:05,120 --> 01:23:06,600 AND HOW MUCH WE SHOULD BE PAYING 2124 01:23:06,600 --> 01:23:07,640 ATTENTION TO THAT. 2125 01:23:07,640 --> 01:23:09,200 BECAUSE OF THIS KNOWLEDGE WE'VE 2126 01:23:09,200 --> 01:23:15,880 IT ITERATED AND HAVE A STUDY 2127 01:23:15,880 --> 01:23:23,240 OPEN HERE AND IN OTHER SITES 2128 01:23:23,240 --> 01:23:25,520 SOON, GD CAR PERSISTS, THE GROUP 2129 01:23:25,520 --> 01:23:27,920 MODIFIED THE CAR ITSELF AND HOW 2130 01:23:27,920 --> 01:23:30,680 WE MAKE IT TO ELIMINATE THIS 2131 01:23:30,680 --> 01:23:37,800 EXHAUSTION, THIS SHOWS THAT THE 2132 01:23:37,800 --> 01:23:42,000 USE OF DEFATINIB, NOT USED FOR 2133 01:23:42,000 --> 01:23:43,400 THIS INDICATION COULD QUIET T 2134 01:23:43,400 --> 01:23:44,920 CELLS WHILE BEING MADE TO LET 2135 01:23:44,920 --> 01:23:46,840 THEM REST AND BE EFFECTIVE WHEN 2136 01:23:46,840 --> 01:23:48,720 THEY GO INTO THE PATIENT, WE'RE 2137 01:23:48,720 --> 01:23:51,680 EXCITED TO SEE HOW THIS WORKS 2138 01:23:51,680 --> 01:23:54,000 GOING FORWARD IN BENCH TO 2139 01:23:54,000 --> 01:23:54,880 BEDSIDE APPROACHES. 2140 01:23:54,880 --> 01:23:56,400 THERE'S MANY CHALLENGES AHEAD. 2141 01:23:56,400 --> 01:23:59,360 I WANT TO REPRESENT THE ENTIRE 2142 01:23:59,360 --> 01:24:01,840 BRANCH, I THINK WE ACCEPT THIS 2143 01:24:01,840 --> 01:24:02,320 CHALLENGE. 2144 01:24:02,320 --> 01:24:03,760 CHALLENGE IS ACCEPTED. 2145 01:24:03,760 --> 01:24:05,120 WE'RE EAGER TO MOVE FORWARD. 2146 01:24:05,120 --> 01:24:08,440 I'M EXCITED TO TELL YOU ABOUT 2147 01:24:08,440 --> 01:24:15,000 DR. NELLEN AND DR. WYNN'S 2148 01:24:15,000 --> 01:24:16,280 EFFORTS IN PRE-CLINICAL WORK AND 2149 01:24:16,280 --> 01:24:18,560 T CELL ENGINEERING IN THE LABS 2150 01:24:18,560 --> 01:24:19,720 AND GOING FORWARD INTO THE 2151 01:24:19,720 --> 01:24:21,480 TRIALS AND I THINK WE WANT TO 2152 01:24:21,480 --> 01:24:24,320 MOVE FORWARD WITH THE NEW 2153 01:24:24,320 --> 01:24:28,720 ENGINEERING, NEW TARGETS, A GPC 2154 01:24:28,720 --> 01:24:32,240 2 TRIAL, NEW EVIDENCE IN BRAIN 2155 01:24:32,240 --> 01:24:38,360 TUMORS, AS WELL AS B7H 3, WE'RE 2156 01:24:38,360 --> 01:24:40,560 EXCITED, AND WE WANT TO 2157 01:24:40,560 --> 01:24:42,360 UNDERSTAND HOW WE CAN TAKE 2158 01:24:42,360 --> 01:24:44,480 ADVANTAGE OF THESE CHALLENGES OF 2159 01:24:44,480 --> 01:24:45,920 THE MICROENVIRONMENT TO OUR 2160 01:24:45,920 --> 01:24:48,000 ADVANTAGE TO MAKE CARs WORK 2161 01:24:48,000 --> 01:24:48,200 BETTER. 2162 01:24:48,200 --> 01:24:49,800 SOME AREAS WE'RE LOOKING AT IS 2163 01:24:49,800 --> 01:24:53,000 NOT JUST ENGINEERING T CELLS BUT 2164 01:24:53,000 --> 01:24:54,240 ENGINEERING MYELOID CELLS TO 2165 01:24:54,240 --> 01:24:56,000 HELP T CELLS WORK BETTER. 2166 01:24:56,000 --> 01:24:57,120 SO WE'RE ACTIVELY ENGAGED IN 2167 01:24:57,120 --> 01:24:57,320 THAT. 2168 01:24:57,320 --> 01:24:59,160 I THINK THE FUTURE FOR OUR WORK 2169 01:24:59,160 --> 01:25:01,560 IS VERY BRIGHT AND I REALLY LOOK 2170 01:25:01,560 --> 01:25:03,960 FORWARD TO LOTS OF CONTINUED 2171 01:25:03,960 --> 01:25:06,960 COLLABORATION ACROSS THE BRANCH 2172 01:25:06,960 --> 01:25:07,400 TO MAKE THIS HAPPEN. 2173 01:25:07,400 --> 01:25:11,400 [APPLAUSE] 2174 01:25:11,400 --> 01:25:13,680 >>DIRECTOR OF HEALTH PSYCHOLOGY 2175 01:25:13,680 --> 01:25:15,040 PROGRAM, PEDIATRIC ONCOLOGY 2176 01:25:15,040 --> 01:25:15,280 BRANCH. 2177 01:25:15,280 --> 01:25:18,080 I'M GOING TO GIVE A BRIEF 2178 01:25:18,080 --> 01:25:19,480 SUMMARY OF THE WORK MY COLLEAGUE 2179 01:25:19,480 --> 01:25:20,880 DR. MARTIN AND I HAVE BEEN DOING 2180 01:25:20,880 --> 01:25:23,560 OVER THE PAST TEN YEARS TO 2181 01:25:23,560 --> 01:25:26,800 ADVANCE ASSESSMENT OF CAR T CELL 2182 01:25:26,800 --> 01:25:28,320 NEUROTOXICITY, SPECIFICALLY 2183 01:25:28,320 --> 01:25:29,160 USING NEURAL COGNITIVE 2184 01:25:29,160 --> 01:25:29,440 EVALUATION. 2185 01:25:29,440 --> 01:25:31,760 THERE IS A HIGH RISK FOR 2186 01:25:31,760 --> 01:25:35,920 DEVELOPING ACUTE SYMPTOMS OF 2187 01:25:35,920 --> 01:25:38,200 NEUROTOXICITY ASSOCIATED WITH 2188 01:25:38,200 --> 01:25:42,280 CRS, CONFUSION, LANGUAGE 2189 01:25:42,280 --> 01:25:43,440 DISTURBANCE, SEIZURES, GENERALLY 2190 01:25:43,440 --> 01:25:44,000 TRANSIENT. 2191 01:25:44,000 --> 01:25:46,200 SYMPTOMS MAY VARY ACROSS 2192 01:25:46,200 --> 01:25:47,720 DIFFERENT THERAPIES, AGES, 2193 01:25:47,720 --> 01:25:49,040 SPECIFIC CANCERS, DOMAINS OF 2194 01:25:49,040 --> 01:25:53,120 FUNCTION, POSSIBLY LONGER 2195 01:25:53,120 --> 01:25:55,560 PERIODS OF TIME. 2196 01:25:55,560 --> 01:25:57,720 UNMET NEEDS TO EVALUATE SYMPTOMS 2197 01:25:57,720 --> 01:25:59,720 OVER TIME FROM ACUTE TO LONG 2198 01:25:59,720 --> 01:26:02,120 TERM, AND COME TO CONSENSUS ON A 2199 01:26:02,120 --> 01:26:04,160 CORE SET OF ASSESSMENT METHODS 2200 01:26:04,160 --> 01:26:07,320 TO COMPARE RESULTS ACROSS TRIALS 2201 01:26:07,320 --> 01:26:08,560 AND GUIDE TREATMENT DECISIONS. 2202 01:26:08,560 --> 01:26:12,920 ABOUT TEN YEARS AGO AT THE 2203 01:26:12,920 --> 01:26:15,040 BEGINNING OF THE TRIAL, DR. 2204 01:26:15,040 --> 01:26:17,080 MAKEEL ASKED US TO DESIGN AN 2205 01:26:17,080 --> 01:26:20,520 EVALUATION TO ASSESS SYMPTOMS OF 2206 01:26:20,520 --> 01:26:20,880 NEUROTOXICITY. 2207 01:26:20,880 --> 01:26:23,600 AT THIS TIME, THERE WERE NO 2208 01:26:23,600 --> 01:26:24,320 SYSTEMATIC NEUROCOGNITIVE 2209 01:26:24,320 --> 01:26:25,840 EVALUATIONS USED IN ANY PREVIOUS 2210 01:26:25,840 --> 01:26:28,400 CAR T CELL TRIALS. 2211 01:26:28,400 --> 01:26:32,040 WE DESIGNED A FOCUSED BRIEF 2212 01:26:32,040 --> 01:26:36,960 NEUROCOGNITIVE TEST BATTERY TO 2213 01:26:36,960 --> 01:26:41,600 EVALUATE DOMAINS IN IN ACUTE 2214 01:26:41,600 --> 01:26:45,600 PHASE, AT BASELINE AND ONE MONTH 2215 01:26:45,600 --> 01:26:47,280 POST-INFUSION. 2216 01:26:47,280 --> 01:26:48,600 IN ADDITION WE DEVELOPED A 2217 01:26:48,600 --> 01:26:51,640 CHECKLIST TO ASSESS BEHAVIORAL 2218 01:26:51,640 --> 01:26:53,400 SYMPTOMS OF NEUROTOXICITY 2219 01:26:53,400 --> 01:26:54,480 EXPERIENCED BY PATIENTS. 2220 01:26:54,480 --> 01:26:57,760 DUE TO POTENTIAL OF SEVERE 2221 01:26:57,760 --> 01:26:58,880 SYMPTOMS DESIGNED A MEASURE TO 2222 01:26:58,880 --> 01:27:01,320 BE COMPLETED BY THE PATIENT'S 2223 01:27:01,320 --> 01:27:03,280 PRIMARY CAREGIVER PRESENT IN THE 2224 01:27:03,280 --> 01:27:05,000 HOSPITAL, BASED ON SYMPTOMS 2225 01:27:05,000 --> 01:27:08,800 OBSERVED IN THE FIRST TRIALS, 2226 01:27:08,800 --> 01:27:11,680 ASSESSES SEVERITY AND DURATION 2227 01:27:11,680 --> 01:27:12,920 OF SYMPTOMS, ADMINISTERED AS 2228 01:27:12,920 --> 01:27:14,400 OFTEN AS NEEDED. 2229 01:27:14,400 --> 01:27:18,120 WE ADMINISTERED AT BASELINE, DAY 2230 01:27:18,120 --> 01:27:24,120 14, ONE MONTH POST-INFUSION. 2231 01:27:24,120 --> 01:27:26,720 ON ALL CURRENT TRIALS. 2232 01:27:26,720 --> 01:27:28,760 WE HAVE FOUND BRIEF EVALUATIONS 2233 01:27:28,760 --> 01:27:34,920 ARE FEASIBLE IN THIS 2234 01:27:34,920 --> 01:27:35,480 POPULATION. 2235 01:27:35,480 --> 01:27:37,080 WE HAVE DEMONSTRATED AVERAGE AND 2236 01:27:37,080 --> 01:27:40,560 STABLE COGNITIVE FUNCTION OF THE 2237 01:27:40,560 --> 01:27:41,600 PEDIATRIC SAMPLES. 2238 01:27:41,600 --> 01:27:43,360 IN ADDITION THE CHECKLIST HAS 2239 01:27:43,360 --> 01:27:45,120 IDENTIFIED AND MONITORED 2240 01:27:45,120 --> 01:27:46,840 SYMPTOMS OVER TIME, BEEN 2241 01:27:46,840 --> 01:27:48,720 SENSITIVE TO CHANGES ASSOCIATED 2242 01:27:48,720 --> 01:27:50,800 WITH CYTOKINE RELEASE SYNDROME, 2243 01:27:50,800 --> 01:27:52,200 AND EXHIBITED INITIAL VALIDITY, 2244 01:27:52,200 --> 01:27:57,480 PATIENTS WITH MORE SEVERE 2245 01:27:57,480 --> 01:28:00,000 SYMPTOMS HAD HIGHER SERUM 2246 01:28:00,000 --> 01:28:00,680 CYTOKINE LEVELS. 2247 01:28:00,680 --> 01:28:02,080 WE'RE STARTING TO CONDUCT A 2248 01:28:02,080 --> 01:28:07,680 PILOT STUDY TO ASSESS ACUTE AND 2249 01:28:07,680 --> 01:28:08,880 LONG-TERM FUNCTIONING. 2250 01:28:08,880 --> 01:28:11,840 THIS TEST BATTERY INCLUDES 2251 01:28:11,840 --> 01:28:13,480 COMPUTERIZED COGNITIVE TEST, 2252 01:28:13,480 --> 01:28:14,920 NEURAL SYMPTOM CHECK LIST, 2253 01:28:14,920 --> 01:28:15,760 ELECTRONIC PATIENT REPORTED 2254 01:28:15,760 --> 01:28:16,160 MEASURES. 2255 01:28:16,160 --> 01:28:17,960 WE INTEND TO USE THE PILOT DATA 2256 01:28:17,960 --> 01:28:20,240 FROM THIS STUDY TO PLAN AND 2257 01:28:20,240 --> 01:28:22,200 OBTAIN FUNDING FOR LARGER 2258 01:28:22,200 --> 01:28:26,800 PERSPECTIVE MULTI-CENTER NEURAL 2259 01:28:26,800 --> 01:28:29,320 TOXICITY TRY TO EXPLORE 2260 01:28:29,320 --> 01:28:30,720 ASSOCIATIONS BETWEEN OUTCOMES SO 2261 01:28:30,720 --> 01:28:32,840 WE CAN BETTER UNDERSTAND OVERALL 2262 01:28:32,840 --> 01:28:35,680 EFFECTS OF CAR T CELL THERAPY IN 2263 01:28:35,680 --> 01:28:36,160 PEDIATRIC POPULATIONS. 2264 01:28:36,160 --> 01:28:38,320 THANK YOU. 2265 01:28:38,320 --> 01:28:40,600 [APPLAUSE] 2266 01:28:40,600 --> 01:28:46,600 2267 01:28:46,600 --> 01:28:52,400 2268 01:28:52,400 --> 01:28:55,000 >> NEXT WE'LL HAVE JAMES GULLEY, 2269 01:28:55,000 --> 01:28:57,320 PRESENTING, AND GIVING A 2270 01:28:57,320 --> 01:29:02,920 PRESENTATION ON THE CENTER FOR 2271 01:29:02,920 --> 01:29:03,280 IMMUNO-ONCOLOGY. 2272 01:29:03,280 --> 01:29:04,000 >> GOOD AFTERNOON, I'M DELIGHTED 2273 01:29:04,000 --> 01:29:07,160 TO TALK TO YOU ABOUT THE CENTER 2274 01:29:07,160 --> 01:29:08,600 FOR IMMUNO-ONCOLOGY. 2275 01:29:08,600 --> 01:29:10,480 I'M JAMES GULLEY. 2276 01:29:10,480 --> 01:29:12,880 THIS CENTER WAS FORMED BY A 2277 01:29:12,880 --> 01:29:14,160 MERGER OF THE LABORATORY OF 2278 01:29:14,160 --> 01:29:15,520 TUMOR IMMUNOLOGY AND BIOLOGY 2279 01:29:15,520 --> 01:29:18,200 WITH COMPONENTS OF THE 2280 01:29:18,200 --> 01:29:20,520 EXPERIMENTAL TRANSPLANTATION AND 2281 01:29:20,520 --> 01:29:23,720 IMMUNOTHERAPY BRANCH, AND THE 2282 01:29:23,720 --> 01:29:26,360 GENITOURINARY MALIGNANCY BRANCH, 2283 01:29:26,360 --> 01:29:28,840 CO-DIRECTED BY DR. SLOWMAN AND 2284 01:29:28,840 --> 01:29:29,200 MYSELF. 2285 01:29:29,200 --> 01:29:31,720 THERE ARE TWO OTHER SENIOR 2286 01:29:31,720 --> 01:29:34,760 INVESTIGATORS, ONE TENURE-TRACK 2287 01:29:34,760 --> 01:29:36,960 INVESTIGATOR, A SENIOR CLINICIAN 2288 01:29:36,960 --> 01:29:40,560 AND A PHYSICIAN-SCIENTIST EARLY 2289 01:29:40,560 --> 01:29:41,080 INVESTIGATOR. 2290 01:29:41,080 --> 01:29:43,160 WE HAVE MULTIPLE ONGOING 2291 01:29:43,160 --> 01:29:45,280 PRE-CLINICAL AND CLINICAL 2292 01:29:45,280 --> 01:29:48,760 EFFORTS WITH IMMUNE CHECKPOINT 2293 01:29:48,760 --> 01:29:50,200 INHIBITORS, IMMUNOCYTOKINES, 2294 01:29:50,200 --> 01:29:51,640 FULL GAMUT OF CELLULAR THERAPY, 2295 01:29:51,640 --> 01:29:52,720 AND BY SPECIFIC ANTIBODIES. 2296 01:29:52,720 --> 01:29:58,840 WE HOPE TO BE ABLE TO ADD IN 2297 01:29:58,840 --> 01:29:59,640 GENETICALLY ENGINEERED MYELOID 2298 01:29:59,640 --> 01:30:03,120 CELLS AS YOU JUST HEARD. 2299 01:30:03,120 --> 01:30:04,560 THERE ARE MULTIPLE COLLABORATION 2300 01:30:04,560 --> 01:30:06,200 OPPORTUNITIES WITH THE CENTER 2301 01:30:06,200 --> 01:30:06,920 FOR IMMUNO-ONCOLOGY. 2302 01:30:06,920 --> 01:30:08,600 IF YOU COLLABORATE WITH US, YOU 2303 01:30:08,600 --> 01:30:10,000 MAY HAVE ACCESS TO NOVEL AGENTS 2304 01:30:10,000 --> 01:30:13,200 TO USE IN THE PRE-CLINICAL OR 2305 01:30:13,200 --> 01:30:15,120 CLINICAL SPACE. 2306 01:30:15,120 --> 01:30:21,920 WE HAVE CRADAs WITH MUST -- 2307 01:30:21,920 --> 01:30:23,920 MULTIPLE COMPANIES, ALL CRADAs 2308 01:30:23,920 --> 01:30:25,960 HAVE THIRD PARTY CLAUSES 2309 01:30:25,960 --> 01:30:28,160 ALLOWING US TO COMBINE 2310 01:30:28,160 --> 01:30:29,360 INVESTIGATIONAL AGENTS FROM 2311 01:30:29,360 --> 01:30:31,960 MULTIPLE COMPANIES IN 2312 01:30:31,960 --> 01:30:33,200 PRE-CLINICAL AND CLINICAL 2313 01:30:33,200 --> 01:30:33,440 STUDIES. 2314 01:30:33,440 --> 01:30:35,240 THERE'S ALSO THE POTENTIAL FOR 2315 01:30:35,240 --> 01:30:36,920 ACCESS TO COLLABORATIVE CLINICAL 2316 01:30:36,920 --> 01:30:37,160 TRIALS. 2317 01:30:37,160 --> 01:30:39,200 WE ACTUALLY COLLABORATE WITH 2318 01:30:39,200 --> 01:30:41,520 MOST OF THE CLINICAL LABS AND 2319 01:30:41,520 --> 01:30:44,680 BRANCHES IN THE CCR ON CLINICAL 2320 01:30:44,680 --> 01:30:45,800 STUDIES. 2321 01:30:45,800 --> 01:30:51,600 THERE'S ACCESS TO COLLABORATIVE 2322 01:30:51,600 --> 01:30:52,200 IMMUNOASSAYS, PERIPHERAL 2323 01:30:52,200 --> 01:30:54,120 IMMUNOPHENOTYPING, LOOKING AT UP 2324 01:30:54,120 --> 01:30:59,680 TO 158 SUBSETS, CAN DO MULTIPLEX 2325 01:30:59,680 --> 01:31:00,440 AND MULTISPECTRAL IMAGING. 2326 01:31:00,440 --> 01:31:02,200 IN THE CENTER FOR 2327 01:31:02,200 --> 01:31:04,280 IMMUNO-ONCOLOGY WE BELIEVE THE 2328 01:31:04,280 --> 01:31:07,600 BEST PATHWAY TO CURE FOR 2329 01:31:07,600 --> 01:31:10,520 PATIENTS IS COMBINATION STUDIES. 2330 01:31:10,520 --> 01:31:13,040 SO, WE REALLY FEEL LIKE YOU NEED 2331 01:31:13,040 --> 01:31:16,120 TO ADDRESS EACH OF THE PARTS OF 2332 01:31:16,120 --> 01:31:20,880 THE TUMOR IMMUNITY CYCLE TO 2333 01:31:20,880 --> 01:31:25,760 GENERATE OR GIVE THE RIGHT CELLS 2334 01:31:25,760 --> 01:31:28,160 TO GROW THEM UP INSIDE THE 2335 01:31:28,160 --> 01:31:29,800 PATIENT, TO ALLOW THEM TO GO TO 2336 01:31:29,800 --> 01:31:31,960 THE TUMOR, TO RECOGNIZE THE 2337 01:31:31,960 --> 01:31:34,160 TUMOR, AND TO REMAIN FUNCTIONAL 2338 01:31:34,160 --> 01:31:38,320 IN THE OFTEN HOSTILE TUMOR 2339 01:31:38,320 --> 01:31:39,920 MICROENVIRONMENT. 2340 01:31:39,920 --> 01:31:41,520 IN ADDITION, IN YOUR CELL 2341 01:31:41,520 --> 01:31:43,040 THERAPY BASED APPROACHES WE'RE 2342 01:31:43,040 --> 01:31:52,320 LOOKING AT GIVING MEMBRANE 2343 01:31:52,320 --> 01:31:56,600 CYTOKINES, TO LOOK AT IL-12, 2344 01:31:56,600 --> 01:31:58,800 IL-15, IL-21, AS WELL AS 2345 01:31:58,800 --> 01:32:00,360 OPPORTUNITIES TO SIGNAL BETTER 2346 01:32:00,360 --> 01:32:02,920 THROUGH THE T-CELL RECEPTOR. 2347 01:32:02,920 --> 01:32:05,040 IN CONCLUSION, I'D LIKE TO THANK 2348 01:32:05,040 --> 01:32:07,000 DR. SHAH FOR INVITING ME TO GIVE 2349 01:32:07,000 --> 01:32:09,520 A LITTLE BIT OF AN OVERVIEW OF 2350 01:32:09,520 --> 01:32:16,240 THE CENTER FOR IMMUNO-ONCOLOGY 2351 01:32:16,240 --> 01:32:19,480 AND THANK HER FOR PUTTING ON 2352 01:32:19,480 --> 01:32:21,720 THIS AMAZING SYMPOSIUM. 2353 01:32:21,720 --> 01:32:22,440 THANK YOU. 2354 01:32:22,440 --> 01:32:23,280 [APPLAUSE] 2355 01:32:23,280 --> 01:32:25,280 >> FOR A VERY FINAL SESSION 2356 01:32:25,280 --> 01:32:27,240 WE'LL END WITH TWO VIDEOS, FIRST 2357 01:32:27,240 --> 01:32:32,280 IS GOING TO BE FROM CRYSTAL 2358 01:32:32,280 --> 01:32:34,280 MAKEL SHARING THOUGHTS. 2359 01:32:34,280 --> 01:32:35,240 SHE'S BEEN A TREMENDOUS 2360 01:32:35,240 --> 01:32:37,120 INSPIRATION TO ALL OF THE WORK 2361 01:32:37,120 --> 01:32:38,760 THAT'S HAPPENED IN THE BRANCH, 2362 01:32:38,760 --> 01:32:44,320 AND, AGAIN, ONE OF OUR POB 2363 01:32:44,320 --> 01:32:44,560 LEGENDS. 2364 01:32:44,560 --> 01:32:46,640 SO CRYSTAL? 2365 01:32:46,640 --> 01:32:49,400 >> I'M CRYSTAL MAKEEL, I WAS AT 2366 01:32:49,400 --> 01:32:54,160 THE PEDIATRIC ONCOLOGY BRANCH 2367 01:32:54,160 --> 01:32:55,160 FROM 1989 UNTIL 2015. 2368 01:32:55,160 --> 01:33:00,240 SO, SPENT A GREAT DEAL OF MY 2369 01:33:00,240 --> 01:33:00,760 LIFE THERE. 2370 01:33:00,760 --> 01:33:06,080 AND IT IS AN ABSOLUTELY 2371 01:33:06,080 --> 01:33:10,000 ESSENTIAL PLACE FOR THE 2372 01:33:10,000 --> 01:33:13,280 EVOLUTION AND PROGRESS IN THE 2373 01:33:13,280 --> 01:33:15,560 REALM OF PEDIATRIC CANCER. 2374 01:33:15,560 --> 01:33:19,040 THE EXPERIENCE WITH CAR T CELLS 2375 01:33:19,040 --> 01:33:22,000 IS JUST ONE EXAMPLE OF SPACE 2376 01:33:22,000 --> 01:33:24,400 WHERE THE PEDIATRIC ONCOLOGY 2377 01:33:24,400 --> 01:33:26,240 BRANCH PLAYED A REMARKABLE ROLE. 2378 01:33:26,240 --> 01:33:28,040 BUT IT'S CERTAINLY NOT THE ONLY 2379 01:33:28,040 --> 01:33:28,240 EXAMPLE. 2380 01:33:28,240 --> 01:33:30,080 I CAN THINK OF MANY. 2381 01:33:30,080 --> 01:33:34,040 BUT TODAY WE'RE HERE TO 2382 01:33:34,040 --> 01:33:35,240 COMMEMORATE THE TEN-YEAR 2383 01:33:35,240 --> 01:33:37,880 ANNIVERSARY OF THE FIRST PATIENT 2384 01:33:37,880 --> 01:33:40,080 TREATED WITH CAR T CELLS IN THE 2385 01:33:40,080 --> 01:33:41,600 PEDIATRIC ONCOLOGY BRANCH. 2386 01:33:41,600 --> 01:33:43,440 I CAN REFLECT BACK A LITTLE BIT 2387 01:33:43,440 --> 01:33:48,800 ON WHAT WAS HAPPENING AT THE 2388 01:33:48,800 --> 01:33:49,720 TIME. 2389 01:33:49,720 --> 01:33:51,440 YOU KNOW, CANCER IMMUNOTHERAPY 2390 01:33:51,440 --> 01:33:54,520 REALLY BLEW WIDE OPEN IN 2010, 2391 01:33:54,520 --> 01:33:57,360 WHEN THE IMMUNE RESPONSES TO NEW 2392 01:33:57,360 --> 01:33:58,560 CHECKPOINT INHIBITORS WERE FIRST 2393 01:33:58,560 --> 01:33:59,600 BEING OBSERVED. 2394 01:33:59,600 --> 01:34:02,200 BUT TO FOLKS IN THE NCI, THIS 2395 01:34:02,200 --> 01:34:03,600 WASN'T A NEW AREA. 2396 01:34:03,600 --> 01:34:07,200 THIS WAS SOMETHING THE NCI HAD 2397 01:34:07,200 --> 01:34:09,160 BEEN WORKING ON FOR CERTAINLY 30 2398 01:34:09,160 --> 01:34:11,800 YEARS, AND IF NOT LONGER. 2399 01:34:11,800 --> 01:34:16,360 NOW, THE GOOD NEWS ABOUT IMMUNE 2400 01:34:16,360 --> 01:34:17,360 CHECKPOINT INHIBITORS IT PUT 2401 01:34:17,360 --> 01:34:19,120 IMMUNOTHERAPY FRONT AND CENTER 2402 01:34:19,120 --> 01:34:21,840 IN CANCER MEDICINE. 2403 01:34:21,840 --> 01:34:24,480 THE BAD NEWS, THEY HAVEN'T HAD A 2404 01:34:24,480 --> 01:34:25,560 TRANSFORMATIVE IMPACT IN 2405 01:34:25,560 --> 01:34:27,080 CHILDHOOD CANCERS. 2406 01:34:27,080 --> 01:34:29,960 SO, ABOUT THE SAME TIME, WE 2407 01:34:29,960 --> 01:34:33,560 STARTED TO SEE THE FIRST SIGNALS 2408 01:34:33,560 --> 01:34:34,840 OF ACTIVITY WITH CD19 CAR T 2409 01:34:34,840 --> 01:34:35,440 CELLS. 2410 01:34:35,440 --> 01:34:36,760 AND I REMEMBER THE FIRST PATIENT 2411 01:34:36,760 --> 01:34:39,360 THAT WAS TREATED ON THE THIRD 2412 01:34:39,360 --> 01:34:41,600 FLOOR BY STEVE ROSENBERG'S 2413 01:34:41,600 --> 01:34:44,480 GROUP, A PATIENT WITH VERY 2414 01:34:44,480 --> 01:34:46,560 REFRACTORY LYMPHOMA. 2415 01:34:46,560 --> 01:34:49,080 AND THIS PATIENT HAD DRAMATIC 2416 01:34:49,080 --> 01:34:49,520 COMPLETE REMISSION. 2417 01:34:49,520 --> 01:34:51,480 AND OF COURSE WORD TRAVELS FAST 2418 01:34:51,480 --> 01:34:53,480 WHEN SOMETHING EXCITING LIKE 2419 01:34:53,480 --> 01:34:54,760 THAT HAPPENS. 2420 01:34:54,760 --> 01:35:04,840 AND WE KNEW THAT UNLIKE 2421 01:35:04,840 --> 01:35:07,680 RITUXIMAB, WHERE IT WASN'T 2422 01:35:07,680 --> 01:35:08,440 WORKING FOR OSTEOSARCOMA, THIS 2423 01:35:08,440 --> 01:35:11,840 WAS ONE OF THE FIRST 2424 01:35:11,840 --> 01:35:12,640 IMMUNOTHERAPIES THAT REALLY, 2425 01:35:12,640 --> 01:35:15,400 REALLY LOOKED LIKE IT WAS 2426 01:35:15,400 --> 01:35:17,000 WELL-SUITED FOR CHILDREN'S 2427 01:35:17,000 --> 01:35:17,240 CANCERS. 2428 01:35:17,240 --> 01:35:18,960 WE IMMEDIATELY GOT TO WORK. 2429 01:35:18,960 --> 01:35:20,240 MY LABORATORY PRETTY MUCH 2430 01:35:20,240 --> 01:35:21,560 DROPPED EVERYTHING IT WAS DOING. 2431 01:35:21,560 --> 01:35:24,280 AND FIGURED OUT HOW WE COULD 2432 01:35:24,280 --> 01:35:27,400 DELIVER CD19 CAR T CELLS TO 2433 01:35:27,400 --> 01:35:28,960 CHILDREN WITH LEUKEMIA. 2434 01:35:28,960 --> 01:35:31,360 AND WE WERE RACING FORWARD. 2435 01:35:31,360 --> 01:35:32,960 WE WERE RACING WITH CHOP, I'LL 2436 01:35:32,960 --> 01:35:34,160 BE HONEST. 2437 01:35:34,160 --> 01:35:36,400 THEY BEAT US BY A FEW MONTHS IN 2438 01:35:36,400 --> 01:35:37,920 TERMS OF TREATING THE FIRST 2439 01:35:37,920 --> 01:35:41,960 PATIENT WHO TURNED OUT TO BE THE 2440 01:35:41,960 --> 01:35:43,400 FAMOUS EMILY WHITEHEAD. 2441 01:35:43,400 --> 01:35:46,840 BUT THE WHOLE COMMUNITY WAS 2442 01:35:46,840 --> 01:35:48,640 REALLY EXCITED ABOUT WHAT THIS 2443 01:35:48,640 --> 01:35:49,720 NEW CLASS OF THERAPEUTICS WAS 2444 01:35:49,720 --> 01:35:51,720 GOING TO SHOW. 2445 01:35:51,720 --> 01:35:54,920 THEY DID NOT DISAPPOINT. 2446 01:35:54,920 --> 01:35:57,920 THERE WERE MANY PATIENTS WHO HAD 2447 01:35:57,920 --> 01:35:58,800 EXHAUSTED ALL STANDARD 2448 01:35:58,800 --> 01:36:01,440 THERAPIES, AND WERE RENDERED 2449 01:36:01,440 --> 01:36:02,440 INTO REMISSION. 2450 01:36:02,440 --> 01:36:04,600 SO IT WAS A PERFECT STORM FORT 2451 01:36:04,600 --> 01:36:06,000 PEDIATRIC ONCOLOGY BRANCH. 2452 01:36:06,000 --> 01:36:07,200 ALL OF THE INFRASTRUCTURE WE 2453 01:36:07,200 --> 01:36:10,520 HAVE FOR DOING CLINICAL TRIALS, 2454 01:36:10,520 --> 01:36:19,360 ALL OF THE REMARKABLE 2455 01:36:19,360 --> 01:36:21,320 IMMUNOLOGY, EXPERTISE WAS JUST 2456 01:36:21,320 --> 01:36:24,520 READY TO APPLY TO THIS ARENA. 2457 01:36:24,520 --> 01:36:26,480 SO THAT WAS THEN. 2458 01:36:26,480 --> 01:36:30,640 TEN YEARS LATER WHERE ARE WE? 2459 01:36:30,640 --> 01:36:32,600 YOU KNOW, I THINK THAT CD19 CAR 2460 01:36:32,600 --> 01:36:34,360 T CELLS WERE APPROVED FOR 2461 01:36:34,360 --> 01:36:37,640 CHILDREN'S CANCER, THAT WAS A 2462 01:36:37,640 --> 01:36:38,600 REMARKABLE ACCOMPLISHMENT. 2463 01:36:38,600 --> 01:36:39,800 BUT THE TRUTH IS THAT WE STILL 2464 01:36:39,800 --> 01:36:41,240 HAVE A LOT OF WORK TO DO. 2465 01:36:41,240 --> 01:36:45,320 LESS THAT BE -- LESS THAN HALF 2466 01:36:45,320 --> 01:36:47,920 OF CHILDREN ARE EXPERIENCING 2467 01:36:47,920 --> 01:36:50,600 LONG-TERM DURABLE CURES. 2468 01:36:50,600 --> 01:36:52,640 AND WE REALLY REMAIN HOPEFUL 2469 01:36:52,640 --> 01:36:56,440 WE'LL BE ABLE TO EXTEND THE 2470 01:36:56,440 --> 01:36:59,240 REACH OF CAR T CELLS BEYOND 2471 01:36:59,240 --> 01:36:59,960 ACUTE LYMPHOPLASTIC LEUKEMIA, 2472 01:36:59,960 --> 01:37:03,600 AND EVIDENCE SAID WE CAN DO 2473 01:37:03,600 --> 01:37:03,800 THAT. 2474 01:37:03,800 --> 01:37:07,440 WE HAVE TO MAKE IT HAPPEN BY 2475 01:37:07,440 --> 01:37:09,840 DOING GREAT FUNDAMENTAL 2476 01:37:09,840 --> 01:37:14,880 RESEARCH, BY DOING RESPONSIBLE 2477 01:37:14,880 --> 01:37:16,520 INNOVATIVE AND RAPID 2478 01:37:16,520 --> 01:37:18,040 TRANSLATION, AND BY SEEING THAT 2479 01:37:18,040 --> 01:37:20,240 THOSE AGENTS THAT HAVE ACTIVITY 2480 01:37:20,240 --> 01:37:22,760 ULTIMATELY FIND A PATH TO 2481 01:37:22,760 --> 01:37:23,520 COMMERCIALIZATION, BECAUSE THOSE 2482 01:37:23,520 --> 01:37:25,400 OF US IN THIS BUSINESS KNOW THAT 2483 01:37:25,400 --> 01:37:27,640 JUST BECAUSE A DRUG IS ACTIVE IN 2484 01:37:27,640 --> 01:37:29,960 CHILDREN DOESN'T MEAN IT WILL 2485 01:37:29,960 --> 01:37:32,440 END UP TO BE A COMMERCIALIZED 2486 01:37:32,440 --> 01:37:34,040 DRUG AVAILABLE FOR TREATMENT 2487 01:37:34,040 --> 01:37:35,720 AROUND THE WORLD. 2488 01:37:35,720 --> 01:37:37,480 WE REALLY WANT OUR DRUGS TO GO 2489 01:37:37,480 --> 01:37:41,720 FROM BENCH TO MARKET. 2490 01:37:41,720 --> 01:37:44,120 NOT JUST BENCH TO BEDSIDE. 2491 01:37:44,120 --> 01:37:46,280 PEDIATRIC ONCOLOGY BRANCH IS 2492 01:37:46,280 --> 01:37:48,240 KEEPING THE TORCH ALIVE, DOING 2493 01:37:48,240 --> 01:37:51,840 AMAZING WORK IN THIS SPACE. 2494 01:37:51,840 --> 01:37:53,000 WE'RE COLLABORATING EXTENSIVELY 2495 01:37:53,000 --> 01:37:55,040 WITH THEM AND WITH MANY 2496 01:37:55,040 --> 01:37:56,840 INSTITUTIONS ACROSS THE COUNTRY, 2497 01:37:56,840 --> 01:37:59,640 HERE AT STANFORD, WE LOOK 2498 01:37:59,640 --> 01:38:02,120 FORWARD TO TAKING THESE 2499 01:38:02,120 --> 01:38:03,360 IMMUNOTHERAPIES TO THE NEXT 2500 01:38:03,360 --> 01:38:06,400 LEVEL AND ALSO TO CONTINUING TO 2501 01:38:06,400 --> 01:38:09,360 ADVANCE THERAPIES FOR CHILDREN'S 2502 01:38:09,360 --> 01:38:11,880 CANCER WRIT LARGE. 2503 01:38:11,880 --> 01:38:13,400 SMALL MOLECULES, DRUGGING THE 2504 01:38:13,400 --> 01:38:16,560 UNDRUGGABLE, A WIDE RANGE OF 2505 01:38:16,560 --> 01:38:19,960 THERAPEUTICS, NOT JUST 2506 01:38:19,960 --> 01:38:20,320 IMMUNOTHERAPY. 2507 01:38:20,320 --> 01:38:21,720 SO CONGRATULATIONS ON, YOU KNOW, 2508 01:38:21,720 --> 01:38:23,920 THE FELLOWSHIP AND I'M SPEAKING 2509 01:38:23,920 --> 01:38:25,840 TO THE NEW FELLOWS HERE. 2510 01:38:25,840 --> 01:38:34,760 THE NIH AND JOHNS HOPKINS ARE 2511 01:38:34,760 --> 01:38:35,920 AMAZING INSTITUTIONS, THE 2512 01:38:35,920 --> 01:38:37,480 PEDIATRIC ONCOLOGY BRANCH IS A 2513 01:38:37,480 --> 01:38:38,560 MAGICAL PLACE. 2514 01:38:38,560 --> 01:38:39,680 THANK YOU, EVERYONE. 2515 01:38:39,680 --> 01:38:41,840 IT'S BEEN GREAT TO TALK TO YOU. 2516 01:38:41,840 --> 01:38:44,040 [APPLAUSE] 2517 01:38:44,040 --> 01:38:49,200 2518 01:38:49,200 --> 01:38:51,720 >> I'LL JUST END IF I COULD HAVE 2519 01:38:51,720 --> 01:38:54,560 THE TEN YEAR CONCLUSION SLIDE. 2520 01:38:54,560 --> 01:38:54,800 YEP. 2521 01:38:54,800 --> 01:38:59,240 AND THE SLIDE DECK IS PERFECT. 2522 01:38:59,240 --> 01:38:59,680 2523 01:38:59,680 --> 01:39:02,440 THANK YOU. 2524 01:39:02,440 --> 01:39:07,440 2525 01:39:07,440 --> 01:39:08,880 SO, AGAIN, I GO BACK TO THIS. 2526 01:39:08,880 --> 01:39:10,080 THIS WORK COULD NOT BE DONE 2527 01:39:10,080 --> 01:39:10,920 WITHOUT YOU. 2528 01:39:10,920 --> 01:39:14,000 I LOOK FORWARD TO WHERE WE WILL 2529 01:39:14,000 --> 01:39:16,920 BE, YOU KNOW, 20 YEARS FROM THE 2530 01:39:16,920 --> 01:39:20,520 FIRST PEDIATRIC CAR T CELL 2531 01:39:20,520 --> 01:39:22,880 EXPERIENCE IN THE POB. 2532 01:39:22,880 --> 01:39:24,160 THERE'S NOT MUCH MORE I HAVE TO 2533 01:39:24,160 --> 01:39:27,680 SAY BUT I'LL END WITH A FINAL 2534 01:39:27,680 --> 01:39:29,000 QUOTE FROM ELIZABETH, DESI'S 2535 01:39:29,000 --> 01:39:29,720 MOM. 2536 01:39:29,720 --> 01:39:31,320 IF IT WASN'T FOR CAR T CELLS, WE 2537 01:39:31,320 --> 01:39:34,040 WOULD NEVER HAVE HAD AN EXTRA 29 2538 01:39:34,040 --> 01:39:36,360 MONTHS ABOUT OUR SON. 2539 01:39:36,360 --> 01:39:37,440 EVERY SINGLE DAY COUNTED. 2540 01:39:37,440 --> 01:39:40,400 THANK YOU TO ALL THE RESEARCHERS 2541 01:39:40,400 --> 01:39:42,480 WORKING HARD IN THE HOPE ONE DAY 2542 01:39:42,480 --> 01:39:43,880 OUR CHILDREN WILL NOT FIGHT 2543 01:39:43,880 --> 01:39:46,280 LEUKEMIA WITH ALL THEIR MIGHT. 2544 01:39:46,280 --> 01:39:48,480 AS I WENT THROUGH THIS I REACHED 2545 01:39:48,480 --> 01:39:51,440 OUT TO MANY FAMILIES, GOING BACK 2546 01:39:51,440 --> 01:39:52,640 A DECADE. 2547 01:39:52,640 --> 01:39:55,360 I HEARD THE EXTRA TIME THEY HAD, 2548 01:39:55,360 --> 01:39:57,680 WE FEEL THEIR LIVES ARE CUT TOO 2549 01:39:57,680 --> 01:39:59,760 SHORT SO I HOPE THERAPY WE'RE 2550 01:39:59,760 --> 01:40:01,400 DOING AND EVERYBODY WHO IS 2551 01:40:01,400 --> 01:40:03,480 INVOLVED AT ANY STAGE OF THIS 2552 01:40:03,480 --> 01:40:05,560 PLATFORM IS ABLE TO SORT OF TAKE 2553 01:40:05,560 --> 01:40:06,440 THIS AS A CHALLENGE TO SAY LET'S 2554 01:40:06,440 --> 01:40:08,640 SEE WHAT WE CAN DO TO REALLY BE 2555 01:40:08,640 --> 01:40:11,200 ABLE TO EXTEND THE LIVES OF THE 2556 01:40:11,200 --> 01:40:12,400 CHILDREN THAT WE TREAT. 2557 01:40:12,400 --> 01:40:15,600 SO WITH THAT, I'LL END WITH A 2558 01:40:15,600 --> 01:40:16,960 BEAUTIFUL SONG THAT ELIZABETH 2559 01:40:16,960 --> 01:40:19,840 HAS OFFERED TO SHARE WITH US AS 2560 01:40:19,840 --> 01:40:20,440 OUR ENDING SLIDE. 2561 01:40:20,440 --> 01:40:23,440 THANK YOU SO MUCH. 2562 01:40:23,440 --> 01:40:29,440 2563 01:40:29,440 --> 01:40:32,360 2564 01:40:32,360 --> 01:40:34,400 AND FINAL VIDEO. 2565 01:40:34,400 --> 01:40:34,640 PERFECT. 2566 01:40:34,640 --> 01:40:37,320 THANK YOU. 2567 01:40:37,320 --> 01:40:43,680 2568 01:40:43,680 --> 01:40:50,160 2569 01:40:50,160 --> 01:40:53,880 [ MUSIC ] 2570 01:40:53,880 --> 01:41:01,560 ♪ YOU LOOK AT ME, AND BABE I 2571 01:41:01,560 --> 01:41:03,360 CATCH ON FIRE ♪ 2572 01:41:03,360 --> 01:41:13,880 ♪ THE STRUGGLE IN MY SOUL ♪ 2573 01:41:40,400 --> 01:41:49,840 [ MUSIC ] 2574 01:41:49,840 --> 01:41:50,120 [APPLAUSE] 2575 01:41:50,120 --> 01:41:52,000 >>THANK YOU, EVERYBODY. 2576 01:41:52,000 --> 00:00:00,000 [APPLAUSE]