Losing his mother to lymphoma and two uncles to melanoma and lung cancer taught James P. Allison, PhD, a difficult lesson at an early age. “My mother was treated with radiation and my uncle, who had lung cancer, was treated with chemotherapy. I saw the ravages of those treatments, which ultimately were unsuccessful,” he says.
Allison knew he wanted to work in cancer research, to create more effective and less toxic treatments. An undergraduate immunology course at the University of Texas at Austin sparked his interest in T cells, warrior cells of the immune system that defend the body against infections and cancer.
In October, Allison won the 2018 Nobel Prize in Physiology or Medicine jointly with Japanese immunologist Tasuku Honjo, MD, PhD. Allison has spent more than 30 years studying how T cells work and what turns the immune response on and off against cancer.
In the 1980s, he discovered the T-cell antigen receptor, which he describes as the cell’s “ignition switch.” A few years later, he showed that a molecule called CD28 acts as the “gas pedal.” Finally, he found that CTLA-4, a protein on the surface of T cells, is the “brake,” signaling the immune system to stop the millions of T cells from attacking the cancer.
The next step, he says, was to prevent the brakes from engaging -- “to give the T cells time to keep going and eliminate the tumors.” Allison’s work led to the development of drugs called checkpoint blockade antibodies, including ipilimumab (Yervoy) for melanoma.
“When we started this work, the median life expectancy with metastatic melanoma was 11 months, and no drug had ever changed that,” he says. Among people treated with Yervoy, more than 20% are still alive 3 years later, and some have survived 10 years.
New drugs targeting another off-switch, PD-1, have since been developed to treat cancers of the head and neck, lung, kidney, and bladder, among others. Now Allison’s lab is studying different combinations of checkpoint blockades to see which patients will respond best to them.
“I don’t think these approaches are going to replace any of the traditional therapies,” he says, but, “I think that soon, immunotherapy is going to be part of every successful cancer therapy.”