A career-long fascination with discovering the ins and outs of T cells, our immune system's tailor-made destroyers of infections and dysfunctional cells, has earned Jim Allison, Ph.D., the American Cancer Society's 2015 Medal of Honor for Basic Research.
Allison's research led directly to new cancer therapies that free the immune system to attack tumors - a breakthrough called immune checkpoint blockade. The professor and chair of Immunology at The University of Texas MD Anderson Cancer Center received the award Wednesday night at a ceremony in Washington, D.C.
"It's a particular honor to receive this recognition from an organization so dedicated to finding cures for cancer," Allison said. "For an immunologist who didn't set out to address cancer, it's also gratifying to see the impact of immunotherapy affirmed by this award."
The drug ipilimumab (Yervoy), developed from Allison's research, became the first treatment to improve the survival of patients with late stage melanoma and was approved for that purpose by the U.S. Food and Drug Administration in 2011. The first-of-its-kind treatment has led to long-term survival, if not cure, of about 20 percent of such patients.
A second type of drug in this class has been approved for melanoma and lung cancer. These drugs are being widely tested against other cancers as single therapies and in combinations.
Drugs unleash immune attack on cancer
Rather than targeting cancer cells directly, they block surface proteins on T cells that turn off immune response, unleashing these white blood cells to seek and destroy cancer.
"Jim Allison's much deserved recognition by the American Cancer Society reminds us that progress against cancer starts with basic scientists who illuminate the details of life at the molecular level," said Ronald A. DePinho, M.D., president, MD Anderson. "Jim's brilliance and avid pursuit of his curiosity about the fundamentals of T cells already have saved the lives of thousands of cancer patients and kept untold numbers of families together. And there is much research and discovery still to come based on his breakthrough."
For decades, research indicated that the immune system could find and kill tumors but was somehow thwarted. Attempts to stimulate the immune system to treat cancer yielded disappointing results. None of that was on Allison's mind as a young scientist at MD Anderson at what is now the institution's Molecular Carcinogenesis department, located at its Research Park in Smithville, Texas.
"T cells had just been discovered and their function was essentially a black box," Allison recalls. "This idea that you had cells cruising all over your body looking for things that had gone awry, maybe a virus infection or a cancer cell, and could destroy those without killing you was pretty amazing."
Allison made a series of discoveries about T cell biology.
At MD Anderson, he identified the T cell receptor, a protein on T cells that serves as the ignition switch of adaptive immune response when specialized immune cells present it with an antigen - bits and pieces of viruses, bacteria, fungi or abnormal host cells.
Later, at the University of California Berkeley, Allison showed that a second protein on T cells called CD28 must be engaged for full activation of T cells, the gas pedal of immune response.
Treat by taking the brakes off T cells
He then helped establish that another molecule on T cells called CTLA-4 acts as a brake on immune response. This led to a crucial insight.
"If we could turn off the brakes for a while we could give the immune system a chance to keep going and eliminate cancer cells," Allison said. "You could treat, not by activating the immune system, but just by taking the brakes off."
He developed an antibody that blocks activation of CTLA-4. In mouse models, the antibody elicited tumor immunity in a variety of cancers. Allison then spent two years actively encouraging pharmaceutical companies to take the approach to the clinic, eventually collaborating with a company called Medarex, which was later purchased by Bristol-Myers Squibb.
Allison moved to Memorial Sloan Kettering Cancer Center in New York to further his research and participate in the drug's progress to clinical trials.
He returned to MD Anderson in 2012 to lead the immunology department and establish the cancer immunotherapy platform, a combination of expertise and infrastructure that brings together scientists and clinicians to better understand and advance cancer immunotherapy.
The platform is part of MD Anderson's Moon Shots Program, which is designed to harness scientific knowledge and cutting-edge technology to dramatically reduce cancer deaths through prevention, early detection and treatment.
Allison holds the Vivian L. Smith Distinguished Chair in Immunology at MD Anderson, is a member of the National Academy of Sciences and the Institute of Medicine. He is a fellow of the American Association for Cancer Research Academy, the American Academy of Microbiology and the American Association for the Advancement of Science. He is co-leader of Stand Up to Cancer's Immunotherapy Dream Team.