TMC PULSE

T M C » P U L S E | N O V E M B E R 2 0 1 8 21 "I have localized disease," he explained. "These immunotherapies— the checkpoint blockades that I developed—start off as experimental therapies that treat the people that have no other alternative. … As with all drugs, the treatments with time are going to move earlier and earlier in the disease." Important questions Allison was born in Alice, Texas, a small town 50 miles west of Corpus Christi. His father was a "country doctor" who helped inspire his son's interest in basic science. Allison lost his mother to lymphoma when he was 10 and cancer also claimed two uncles. The budding scientist witnessed the ravages of radiation and chemotherapy at an early age. As a young man, Allison grew interested in the role T cells played in the immune system. After finishing his bachelor's degree in micro- biology and a doctorate in biological sciences at The University of Texas at Austin, Allison first worked for MD Anderson at its science park in Smithville, Texas, where he began unraveling the mysteries of T cells from 1977 to 1984. He took a sabbatical to Stanford University to continue his research. "He slept on my couch on and off for the next year. We got to be good friends," said Lewis Lanier, Ph.D., now chair of the department of microbiology and immunology at the University of California, San Francisco. The pair had bonded a few years earlier during a week of extracurricular skiing and wine-drinking at a lymphoma conference. "We started doing things scientifically together related to under- standing the T cell receptor and we published some nice papers together during that time," Lanier said, noting that Allison eventually WHAT IS IMMUNOTHERAPY? Immunotherapy is a type of treatment that trains the immune system to attack cancer. Immune system cells—including T cells (so-called because they develop in a small organ called the thymus gland) and antigen-presenting cells (APCs)—defend and protect the body. APCs patrol the body and T cells are the soldiers of the immune system. When an APC finds something suspicious, it sends a signal to a T cell to multiply and attack the suspicious cells. But if T cells don't stop multiplying, they can damage healthy cells, so a safety switch in the T cell, called a checkpoint, prevents this. Because cancer is so complex, though, T cells are switched off before their work fighting cancer is done. Checkpoint inhibitor drugs, the most common type of immunotherapy, can prevent T cells from being switched off. This allows T cells to fight cancer. Immunotherapy also helps the immune system remember so the T cells can quickly target the cancer if it returns. WHAT CONTRIBUTION TO IMMUNOTHERAPY EARNED JAMES ALLISON A NOBEL? Allison blocked a protein on T cells that acts as a brake, thus freeing T cells to attack cancer. Specifically, Allison developed an antibody to block the checkpoint protein CTLA-4. His work led to the devel- opment of the first immune checkpoint inhibitor drug, ipilimumab, known commercially as Yervoy. Source: The University of Texas MD Anderson Cancer Center jumped from Smithville to the University of California, Berkeley. "Then we got to be really close friends." Over the next two decades, Lanier and Allison collaborated profes- sionally while celebrating holidays at each other's homes. Their families vacationed together. During this period, Allison honed his love of the blues and country music as a harmonica player who performed with The CheckPoints, a band composed of immunologists and oncologists. For years, Lanier has set his alarm to wake in the wee hours for the Nobel Prize announcement in medicine—and then gone back to sleep. This year, Lanier stayed wide-eyed and rang his longtime friend to offer congratulations. "It's so well deserved. There really would not be this new check- point blockade therapy without him," Lanier said. "Jim always asked: 'What is the important question to pursue?' And then he'd go after that doggedly. He did that with the T cell receptor. He did that with what is known as co-stimulation—identifying the turbocharge for the second segment of T cells—and then when he had the idea of blocking the inhibitors of the T cells to apply that to cancer. Those were three huge questions that he managed to address." Driven to find the truth Antoni Ribas, M.D., Ph.D., a professor of medicine at the University of California, Los Angeles (UCLA), met Allison in the mid-2000s after making a presentation at an American Society of Clinical Oncology meeting. Ribas had used a CTLA-4-blocking antibody in patients and was sharing the results. (continued)

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