CD19 CAR T cells and the living drug concept

Michel Sadelain, MD, PhD
Director
Center for Cell Engineering
Sloan Kettering Institute
New York, NY, USA

This conference is hosted by Hua Gu, PhD. This conference is part of the 2023-2024 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

About this conference
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to engage and eliminate cancer cells. CARs that target CD19 have produced remarkable responses in patients with refractory B cell malignancies. To date, four CD19 CAR therapies are approved by the US FDA. Despite high complete remission rates in patients with refractory B cell malignancies, a number of patients will eventually relapse. 

Recent studies on the antigen sensitivity of CAR T cells have yielded valuable insights into the antigen density requirements and the role of scFv affinity and costimulatory structures incorporated into CARs to enhance tumor recognition and limit antigen escape. A novel family of CARs, termed HIT receptors, provides greater sensitivity, allowing to target tumors that escape conventional CARs. Logic-gated CAR T cells offer the prospect of more selective tumor targeting, exemplified by IF-BETTER gating. Novel CAR designs, such as 1XX, reconcile the effector potency of CD28-based CARs with the greater T cell persistence afforded by 4-1BB based CARs. Genome editing adds a valuable tool to transcriptionally control CAR expression, remodel the T cell receptor and target a variety of pathways, including epigenetic programming to extend the functional persistence of immune effector cells. 
 
CAR T cells thus embody a novel paradigm for immunotherapy, based on the genetic instruction of cellular immunity using synthetic receptors and in some instances genome editing, thereby providing “living drugs” to patients who otherwise fail to generate effective immunity.

About Michel Sadelain
Michel Sadelain, MD, PhD, is the Director of the Center for Cell Engineering and the incumbent of the Stephen and Barbara Friedman Chair at Memorial Sloan Kettering Cancer Center. He is a Member of the Immunology Program and the Department of Medicine. 
     
Dr. Sadelain’s research focuses on human cell engineering and cell therapy to treat cancer and hereditary blood disorders. His laboratory has made several seminal contributions to the field of chimeric antigen receptors (CARs), from their conceptualization and optimization to their clinical translation for cancer immunotherapy. His group identified CD19 as a potential target for CAR therapy and was the first to report dramatic molecular remissions obtained with CD19-targeted CAR T cells in patients with refractory acute lymphoblastic leukemia.
    
Dr. Sadelain is the recipient of the Cancer Research Institute’s Coley Award for Distinguished Research in Tumor Immunology, the Sultan Bin Khalifa International Award for Innovative Medical Research on Thalassemia, the NYPLA Inventor of the Year award, the Passano award, the Pasteur-Weizmann award, the Gabbay award, the INSERM International Prize Laureate, the ARC Foundation Léopold Griffuel award, the Outstanding Achievement Award from the American Society for Gene and Cell Therapy, the Clarivate Citation Laureate in Physiology or Medicine for breakthrough research advancing CAR therapy for the treatment of cancer and most recently the 2024 Breakthrough Prize in Life Sciences. He previously served on the NIH Recombinant DNA Advisory Committee and as President of the American Society for Gene and Cell Therapy.

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