TMC PULSE

T M C » P U L S E | N O V E M B E R 2 0 1 8 19 Below: A crowd congratulates James Allison, Ph.D., at The University of Texas MD Anderson Cancer Center in October. T hrough weeks of international acclaim, with highlights that included an early-morning phone call from Sweden and a homecom- ing parade through the halls of MD Anderson, James Allison, Ph.D., insisted that he never set out to find a new way to treat cancer. As a basic scientist, Allison arrived at immu- notherapy by way of T cells. "I've always been interested in the immune system and, in particular, a very specific part of it called T cells. These are cells that, to me, are just amazing," Allison said. "They go all through your body looking for infection or cancer, we know now, and respond to it by generating an army of similar soldiers who can attack … in a way that doesn't harm normal cells. I've been intellectually challenged by the wonderful complexity of that." Allison was awarded the 2018 Nobel Prize in Physiology or Medicine jointly with Japanese immunologist Tasuku Honjo, M.D., Ph.D., for the discovery of cancer therapies that stimulate the immune system to attack tumor cells. Treatments developed from Allison's work have extended the lives of thousands of people with advanced disease, though certain cancers have responded better to immunother- apy than others. "A few cancers, like glioblastoma and pancreatic cancer, thus far, Credit: Akademie / Alamy Stock Photo have not responded at all," Allison said. "There's a lot more hard work to be done." Both Allison, 70, and Honjo, 76, made discoveries that led to the development of "checkpoint inhibitors," drugs infused into patients to block molecules that put the brakes on T cells. By releasing these brakes, the body's own immune system is able to fight cancer. Allison recognized that a protein on T cells called CTLA-4 stopped their ability to fight disease. By inhibiting that checkpoint— or releasing the brakes—he found that the T cells could be unleashed to attack tumors. Allison developed an antibody to block CTLA-4, which turned into the drug ipilimumab, now used to fight metastatic melanoma. Known commercially as Yervoy, the drug was approved in 2011 by the U.S. Food and Drug Administration (FDA) and has delivered unprecedented results. Honjo, of Japan's Kyoto University, also discovered a protein on immune cells that serves as a brake—the checkpoint molecule PD-1. In 2014, the FDA approved the drugs Keytruda and Opdivo, which inhibit PD-1 for the treatment of metastatic melanoma. In March 2015, Opdivo was approved for lung cancer treatment. (continued)

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