Michel Sadelain is Director of the Columbia Initiative in Cell Engineering and Therapy (CICET) and Director of the Cancer Cell Therapy Initiative in the Herbert Irving Comprehensive Cancer Center at Columbia University. He joined Columbia University from Memorial Sloan Kettering Cancer Center (MSK) where was the founding director of the Center for Cell Engineering. He received his M.D. from the University of Paris (Pierre et Marie Curie) in 1984 and his Ph.D. from the University of Alberta (Edmonton) in 1989. Following his post-doctoral research at the Whitehead Institute at MIT, he joined MSK in 1994. Dr Sadelain founded the Center for Cell Engineering in 2008.
Sadelain has made several key contributions to the emergence and success of CD19 chimeric antigen receptor (CAR) therapy. His research contributed to all facets of CAR therapy, including T cell engineering methodologies (via retroviral vectors or gene editing), CAR design (dual-signaling receptor concept, known as second generation CAR), the identification of CD19 as an effective CAR target, T cell manufacturing (GMP processes, in collaboration with Dr. Isabelle Rivière at MSK) and clinical translation (in acute lymphoblastic leukemia and other cancers).
In 1992, Sadelain reported the first successful genetic engineering of primary T cells. In 2002, his lab was the first to report the design of receptors for antigen that comprise both activating and costimulatory domains, thereby enabling the generation of effective therapeutic T cells from peripheral blood cells. All current FDA-approved CARs follow this dual-signaling paradigm. In 2003, Sadelain identified CD19 as an optimal CAR target and provided the first experimental evidence that engineered human T cells could eradicate CD19+ lymphomas and leukemias in mice. After establishing cGMP vector production and CAR T cell manufacturing at MSK, Sadelain and his team reported in 2013 the first dramatic responses to CD19 CAR therapy in adults with relapsed and refractory ALL, highlighted in Science’s “Scientific breakthrough of the year” and later earning FDA’s “Breakthrough designation”. The Center for Cell Engineering team has by now treated >550 patients with CAR T cells produced at MSK.
CD19 CAR therapy is a true paradigm shift: it has not only changed the standard of care for B cell malignancies but ushered a new class of drugs (engineered T cells directed by synthetic receptors, which Dr Sadelain nicknamed “living drugs”) and served as a catalyst for evolution in the pharmaceutical industry (which had not embraced cell-based medicines before the advent of CD19 CAR T cells). There are today >100 potential CAR targets reported in the literature, >1000 CAR trials listed at clinicaltrials.gov. CARs are now investigated worldwide for cancer, infectious diseases, autoimmunity and senescence-associated pathologies. CAR T cells targeting CD19 have shown promising early results for the treatment of systemic lupus erythematosus.
Dr. Sadelain remains very engaged in CAR research, combining basic innovation and clinical relevance to pursue the goal of making CAR therapy more effective, more broadly applicable and safer. His lab has modeled and unraveled some of the mechanisms of CAR toxicity, augmented the potency of CAR T cells based on signaling, genome editing and epigenetic programming and demonstrated that CAR T cells could be derived from pluripotent stem cells, which may eventually forego the need to collect and process T cells from patients.
Michel 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, Gabbay, Pasteur-Weizman/Servier and Leopold Griffuel awards, the INSERM International Prize, the Breakthrough Prize for Life Sciences and the Gairdner International Award. He previously served as President of the American Society for Gene and Cell Therapy.
