Dedication. For his work developing a new form of therapy called CAR-T that is highly effective against certain types of blood cancer, Michel Sadelin, a 63-year-old immunologist, received a Breakthrough Award, nicknamed the “Oscar of Science.”
“You can’t imagine how many times I’ve heard that it won’t work, and that even if it did, there’s no future for him,” the doctor told AFP. When he began his research into programming immune cells to fight cancer, many skeptical colleagues tried to dissuade him, including his own mother, who was worried about his career. Some scholarships elude him, promotions become uncertain, and students largely avoid his laboratory.
Award founded by Silicon Valley entrepreneurs
The Breakthrough Prize was created by Silicon Valley entrepreneurs in the early 2010s to reward breakthroughs in basic research. Awarding a total of more than $15 million, it is the largest scientific prize, surpassing the Nobel Prize.
“I’ll have to throw a big party to thank everyone who contributed to this concept,” laughs the researcher today, who will share $3 million with American Carl June, an immunologist who also worked on the topic on his side.
Development of cancer vaccines
Michel Sadelin studied medicine in Paris and then immunology in Canada before accepting a postdoctoral position at the Massachusetts Institute of Technology (MIT) in 1989. At that time, the idea of developing cancer vaccines arose because vaccines existed. targeting bacteria and viruses are attracting a lot of interest.
“But I started thinking that maybe we should directly program fighters into our immune system, especially T cells,” he explains. His work began on mice.
Joining Memorial Sloan-Kettering Cancer Center in New York, he developed a way to genetically reprogram human T cells using viral vectors. The latter then acquire receptors that can recognize and fight cancer cells.
These receptors, which he calls chimeric antigen receptors (CARs), also direct the proliferation of T cells to swell the army of little soldiers needed to fight the disease. The patient’s T cells are first collected, modified outside the body, and then reintroduced into the bloodstream, becoming “living drugs.”
In a recent clinical study of a type of cancer called multiple myeloma, 28% of patients had their disease go away after taking this treatment. Of these, 65% were free of relapse after 12 months. Thanks to the work of Michel Sadelin and Carl June, half a dozen treatments using this method have been approved in the United States, and hundreds of other clinical trials are underway.
However, the treatment can have serious side effects due to the triggering of an inflammatory response, which in some cases can lead to death. But doctors have learned to recognize and contain this effect. Neurological effects such as severe confusion or inability to speak may also occur, but these resolve within a few days.
Michel Sadelin remains enthusiastic about the future of the therapy, which could be used against other cancers, autoimmune diseases or refractory infections such as HIV in the future, he said. But he admits another improvement is needed: its high price tag, which now tops $500,000. In the United States, as in Europe, insurance covers most of the bill.
“The researchers were shocked”
“Researchers were shocked when they saw the amount charged for the very first treatments,” he said. The price should come down. He expects this to happen as the pharmaceutical industry improves its processes and through scientific innovations in the production and quality of chimeric antigen receptor T cells (or CAR-T cells).
His own laboratory, for example, is preparing to publish a study showing that the new model can reduce the number of lymphocytes needed for treatment. Other researchers are exploring the possibility of producing CAR-T cells from stem cells, which may be less expensive.