NIH VideoCast - Driving CARs to BARs: The Road to Engineered Specific Human T Regulatory Cells

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Driving CARs to BARs: The Road to Engineered Specific Human T Regulatory Cells

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Air date:	Wednesday, June 15, 2016, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 487 (66 Live, 421 On-demand)
Category:	Immunology
Runtime:	01:04:09
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group David W. Scott, Ph.D. is Vice Chair for Research in the Department of Medicine at the Uniformed Services School of Health Sciences, Bethesda, MD. An alumnus of Antioch College, he received his M.S. degree from the University of Chicago and Ph.D. from Yale University in 1969. Following a post-doctoral fellowship at Oxford University, he has held tenured faculty positions at Duke University, the University of Rochester, and the University of Maryland Medical School. He assumed his current position in September 2010. Dr. Scott has contributed to over 200 research papers on several subjects on immunologic tolerance, and its application in autoimmune diseases, hemophilia and gene therapy. He is the author of two textbooks, including The Nature of Immunologic Tolerance, and recipient of a number of awards, e.g. Distinguished Service Award from the American Association of Immunologists, a Boarhaave Professorship at Leiden University in Holland, and the 2009 Scientific Achievement Award from AAPS. Abstract: Clinical application of expanded T regulatory cells (Tregs) offers great promise for the treatment of undesirable immune responses. However, treatment with polyclonal Tregs, which are not specific for a single epitope, could potentially lead to global immunosuppression. We have engineered human T cells to express chimeric antigen receptors (CARs) using either T-cell receptors from MS or hemophilia patients or specific single chain Fv’s. Thus, we adapted the CAR approach utilized successfully for leukemia therapy (e.g. CD19 CAR CD8's) to create specific T regulatory cells recognizing myelin basic protein (for MS) or FVIII, in the case of hemophilia. Such cells can actively suppress effector T cell proliferation and cytokine formation, as well as antibody formation in vitro. Further development with B-cell targeting strategies have also been successful by expressing antigen domains in CD8 T cells that kill B cells specific for FVIII, for example. Application of these engineered T cells to modulate adverse antibody responses in hemophilia and pathogenic responses to CNS proteins will be presented, and the mechanisms further discussed.

NLM Title:	Driving CARs to BARs : the road to engineered specific human T regulatory cells / David W. Scott ; Immunology Interest Group.
Author:	Scott, David W. National Institutes of Health (U.S.). Immunology Interest Group,
Publisher:
Abstract:	(CIT): David W. Scott, Ph.D. is Vice Chair for Research in the Department of Medicine at the Uniformed Services School of Health Sciences, Bethesda, MD. An alumnus of Antioch College, he received his M.S. degree from the University of Chicago and Ph.D. from Yale University in 1969. Following a post-doctoral fellowship at Oxford University, he has held tenured faculty positions at Duke University, the University of Rochester, and the University of Maryland Medical School. He assumed his current position in September 2010. Dr. Scott has contributed to over 200 research papers on several subjects on immunologic tolerance, and its application in autoimmune diseases, hemophilia and gene therapy. He is the author of two textbooks, including The Nature of Immunologic Tolerance, and recipient of a number of awards, e.g. Distinguished Service Award from the American Association of Immunologists, a Boarhaave Professorship at Leiden University in Holland, and the 2009 Scientific Achievement Award from AAPS. Abstract: Clinical application of expanded T regulatory cells (Tregs) offers great promise for the treatment of undesirable immune responses. However, treatment with polyclonal Tregs, which are not specific for a single epitope, could potentially lead to global immunosuppression. We have engineered human T cells to express chimeric antigen receptors (CARs) using either T-cell receptors from MS or hemophilia patients or specific single chain Fv"s. Thus, we adapted the CAR approach utilized successfully for leukemia therapy (e.g. CD19 CAR CD8's) to create specific T regulatory cells recognizing myelin basic protein (for MS) or FVIII, in the case of hemophilia. Such cells can actively suppress effector T cell proliferation and cytokine formation, as well as antibody formation in vitro. Further development with B-cell targeting strategies have also been successful by expressing antigen domains in CD8 T cells that kill B cells specific for FVIII, for example. Application of these engineered T cells to modulate adverse antibody responses in hemophilia and pathogenic responses to CNS proteins will be presented, and the mechanisms further discussed.
Subjects:	T-Lymphocytes, Regulatory--immunology
Publication Types:	Lecture Webcast

NLM Classification:	QW 568
NLM ID:	101686964
CIT Live ID:	19315
Permanent link:	https://videocast.nih.gov/watch=19315

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