Alfred E. Mann Department of Biomedical Engineering

Speaker: Michel Sadelain, MD, Ph.D., Director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center

Talk Title: CD 19 CAR T cells: A paradigm for the living Drug Concept

Abstract: Natural immune responses fall short of eradicating tumors in most cancer patients. The genetic engineering of T cells offers a means to repurpose immune cells to remedy these limitations. The first successful embodiment of engineered immunity is chimeric antigen receptor (CAR) therapy targeting CD19. CARs are synthetic receptors that redirect and reprogram T cells to engage and eliminate cancer cells. CARs that target CD19, a cell surface molecule found in most leukemias and lymphomas, have produced remarkable responses in patients with refractory B cell malignancies. Four CD19 CAR therapies are currently approved by the US FDA. Over 1000 CAR therapy trials are currently listed on the clinicaltrials.gov website.  Despite high complete remission rates obtained following a single CAR T cell infusion in patients with relapsed hematological malignancies, a number of patients will eventually relapse, pointing to the need to further improve CAR design and T cell engineering strategies to increase the antigen sensitivity and functional persistence of CAR T cells. 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, aim to reconcile the effector potency of CD28-based CARs with the greater T cell persistence afforded by 4-1BB based CARs. Genome editing is emerging as a valuable tool to transcriptionally control CAR expression, remodel the T cell receptor (TCR) and enable epigenetic programming to extend the functional persistence of immune effector cells.  CAR T cells thus embody a novel paradigm for immunotherapy, providing “living drugs” for patients who fail to generate effective tumor immunity through active immunization or checkpoint blockade. The success of CD19 CAR therapy in cancer further provides a foundation for evaluating CAR T cells in other pathologies such as senescence-associated disorders and autoimmunity.    

Biography: 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. 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 design to clinical translation. His group was the first to publish dramatic molecular remissions in patients with chemorefractory acute lymphoblastic leukemia following treatment with CD19 CAR T cells.

Host: Peter Wang, Dr. Lerman, Dr. C. Meltzer

More Info: https://usc.zoom.us/j/91924460032

Location: Harlyne J. Norris Research Tower (NRT) - Aresty Auditprium HSC

Audiences: Everyone Is Invited

Contact: Carla Stanard

Event Link: https://usc.zoom.us/j/91924460032