BIO
Michel Sadelain (Paris, France, 1960), of French and Canadian nationality, earned his medical degree at the University of Paris (1984), before going on to complete a PhD in Immunology at the University of Alberta (Canada) in 1989, followed by a postdoctoral fellowship at the Whitehead Institute for Biomedical Research of Massachusetts Institute of Technology. In 1994 he joined the Memorial Sloan Kettering Cancer Center in New York, where he was the Stephen and Barbara Friedman Chair, founding director of the Center for Cell Engineering and head of the Gene Transfer and Gene Expression Laboratory. In 2024 he moved to Columbia University, also in New York, where he is currently Herbert and Florence Professor of Medicine, Director of the Columbia Initiative in Cell Engineering and Therapy and Director of the Cancer Cell Therapy Initiative at the Herbert Irving Comprehensive Cancer Center. A past president of the American Society of Gene and Cell Therapy, he has also served on the Recombinant DNA Advisory Committee of the National Institutes of Health. Sadelain has authored over 280 published papers and his research has resulted in more than 60 patents.
CONTRIBUTION
“We are fortunate to have an immune system that protects us from invaders like viruses, parasites or bacteria. But when it comes to cancer, even this wonderful system is not always up to the challenge,” Michel Sadelain explains. In the early 1990s, while at the Memorial Sloan Kettering Cancer Center in New York, it was precisely this challenge that got the French-Canadian researcher thinking of ways to “help this immune system of ours by means of genetic engineering, teaching the all-important T cells to recognize cancer cells and then eliminate them.”
Building on the findings of Israeli researcher Zelig Eshhar (d. 2025), who first proposed the chimeric antigen receptors (CAR) concept in 1993, Sadelain set out to establish the feasibility of the technique. Eshhar had developed a first generation of CARs – synthetic proteins designed in the lab that are added to T cells using genetic modification – but they proved unable to survive in any organism.
In 2002, after ten years of research, Sadelain and his team managed to engineer what were known as second-generation CAR-T cells, capable of surviving, proliferating, and killing cancer cells in vitro in the lab, thereby proving the viability of producing genetically instructed, targeted immune responses. “When we introduce a CAR into a T cell,” says Sadelain, “it acquires the ability to recognize tumor cells and will then proceed to destroy them.”
One year later, in 2003, he and his colleagues published a research paper in Nature Medicine showing that human CAR T cells targeting a protein known as CD19 – expressed in leukemias and lymphomas – could eradicate these malignant cells in mice.
Sadelain explains that when the CD19 molecule was identified as a target for CAR-T therapy in blood cancers, “we knew that a side effect would be to eliminate not only leukemias or lymphomas, but also normal B cells, the cells that produce antibodies.” As a rule, antibodies play a vital role in protecting us against infections and other diseases, but in some circumstances they can also turn against us, attacking our own tissues. This is precisely what happens in patients suffering autoimmune disorders like lupus, and it has recently been found that CAR-T cells designed to act against the CD19 molecule that is a target for leukemia can also serve for this kind of condition.
“Remarkably, marvelously,” Sadelain enthuses, “they immediately achieved complete responses in lupus patients.” And this success has set in motion “a wave of new clinical studies in the worlds of rheumatology and neurology,” to see whether CAR-T cells might be effective in controlling autoimmune diseases like arthritis and multiple sclerosis.
“June and Sadelain have brought about a paradigm shift in modern medicine with the development of CAR-T cell immunotherapy. Their work has profoundly transformed the fields of oncology and immunology, to the extent that they are considered the fathers of the first ‘living drug’ in medical history. Unlike traditional drugs, which are metabolized over time and require repeat doses, CAR-T cells comprise the patient’s own cells, which, after being genetically modified to selectively recognize and destroy tumor cells, can persist and function in the body for years, such that a single dose can provide lasting protection. Genetic engineering provides a level of precision that chemotherapy cannot achieve. While the latter acts in a non-selective manner, CAR-T cells attack only the target cells and leave healthy tissue untouched,” explains Antonio Pérez-Martínez, Head of the Pediatric Hemato-Oncology Department at Hospital Universitario La Paz and another nominator of the winning entry.
