Research Day: Crafting Cancer-Killing Drugs

Michael Doche (left), PhD, project scientist in the Cedars-Sinai Biobank and Translational Research Core, explains his research on a new method of collecting prostate tissue to Joshua Saylor, research associate in the laboratory of Beatrice Knudsen, MD, PhD, medical director of the biobank.

Sadelain, director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at Memorial Sloan Kettering Cancer Center in New York, helped forge the future of immunotherapy—which harnesses the immune system to fight diseases—by proving that human cells can be transformed into cancer-killing drugs.

This milestone achievement was nearly 30 years in the making, Sadelain explained. It began in the 1990s, when as a postdoctoral student at the Massachusetts Institute of Technology, he was intrigued by innovative genetic engineering tools designed to introduce genes into T cells—a type of immune-response cell—with the goal of creating cancer fighters.

In 2002, Sadelain and his research team demonstrated that T cells can be removed from a patient and then genetically engineered to produce chimeric antigen receptors (CARs) on the cells' surface. CARs are synthetic receptors that arm T cells with proteins capable of recognizing cancer. The genetically engineered T cells, when returned to the patient through infusion, not only kill tumor cells—they persist in the body as "living drugs." CAR T-cell therapy was born.

The next year, Sadelain's team published a seminal paper demonstrating that CAR T cells equipped with a protein known as CD19 could fight leukemia in a mouse model. "We then set out to translate our mouse-model success to the clinic," Sadelain said. They achieved their goal last year when the U.S. Food and Drug Administration (FDA) approved CD19 CAR T-cell therapy for treatment of acute lymphoblastic leukemia in certain children and young adults and also for certain patients with non-Hodgkin lymphoma.

Most recently, in the Feb. 1 issue of the New England Journal of Medicine, Sadelain and colleagues published results of a phase 1 clinical trial of 53 adults with acute lymphoblastic leukemia who received CD19 CAR T-cell therapy. Complete remission was achieved in 83 percent of these patients.

While tremendous strides have been made in CAR T-cell therapy, Sadelain said challenges remain, including managing side effects and applying the approach to more types of cancer.

Michel Sadelian MD of the Memorial Sloan Kettering Cancer Institute

Keynote speaker Michel Sadelain, MD, PhD, discusses one of several immunotherapy breakthroughs he pioneered.