A cure for cancer. Few possibilities can so swiftly unbridle humanity of its preoccupations. Jim Allison has our attention. Allison effects the timbre of a mellow, country-band harmonica player who performed on stage with Willie Nelson. And on the weekends he is that. The rest of the time, he’s a Nobel Prize-winning researcher at the University of Texas MD Anderson Cancer Center in Houston, where treatments based on his discoveries regularly save lives. Even his easy going demeanor cracks with emotion when recounting one of his first cancer patients, a 22-year-old woman with more than 30 tumors in her lungs, brain, and skin. She was hospice bound, but is now cancer-free. But Allison is not an oncologist. He’s an immunologist. Cancer cells routinely arise in your body. However, immune system cells called T cells usually neutralize them before they turn into masses. But sometimes the immune system falls behind. The research Allison started in the late 1980s explained this phenomenon by uncovering a mechanism by which the body naturally blocks its cancer-killing T cells. Allison then discovered a way to chemically inhibit that suppression, enabling the body to produce a surge of T cells that work to eliminate the cancer. Allison’s groundbreaking research directly led to ipilimumab, an injectable drug with a high success rate in curing several common cancers, including melanoma, even at end stages. But Allison believes immunotherapy can do even more. He’s currently researching the possibility of enhanced immunotherapy drugs capable of curing a broad spectrum of cancers, hopeful for a future when second chances happen without the side effects of chemotherapy and radiation or the invasive surgeries that we rely on today.
Sharon Belvin was diagnosed with melanoma just weeks before her wedding. She had more than 30 metastatic tumors in her lungs, brain, and skin. Standard drugs had failed and, hospice-bound, she enrolled in a clinical trial led by Jim Allison in a final effort to save her life. Six months after her initial treatment, the tumors were gone. A decade later, now a fitness instructor and mother of two, Sharon is still cancer-free.
It is for patients like Sharon that Jim Allison persists in searching for cures for cancer. A Nobel Prize-winning immunologist and researcher at the University of Texas MD Anderson Cancer Center in Houston, Allison is one of the first scientists to observe the role of the immune system in fighting cancer and to prove that blocking the body’s normal “stop signals” to an immune response could shrink or even eradicate tumors.
Allison’s brilliance was inspired by his upbringing in Alice, a small town in South Texas. He spent his days in the garage with his chemistry set and joined his father, a country doctor, on house calls. He likes to say that his father was the first immunologist he knew and has childhood memories of being intentionally exposed to chicken pox to build his immune system. But Allison’s memories of that time were not all positive. As a boy, he observed how the radiation treatments and chemotherapy used to treat his mother’s lymphoma ravaged her body. As a result, Allison has a special understanding of cancer and the effects of invasive cancer treatments, and a powerful drive to find a cure.
Allison attended the University of Texas, Austin with an eye towards medical school, but found the problem-solving of bench science a better fit, and earned his Ph.D. in biological sciences from UT in 1973. His interest in immunology and the mechanisms that underlie the immune response intensified. In particular, Allison hoped to better understand the function of immune system cells called T cells. At the time, it was known that T cells circulated throughout the body, searching for and killing invading bacteria and viruses without damaging normal cells. But questions remained: How do T cells recognize invaders? How are they activated and inactivated?
This initial phase of Allison’s research led to important discoveries. He and his colleagues identified a T-cell antigen receptor—a molecule found on the surface of T cells—responsible for recognizing invaders and triggering an immunological response. Their experiments led to the breakthrough realization that the T cell requires two signals for full activation: one from the antigen receptor and another ‘confirmatory’ signal to authenticate the response. Allison likens them to the ignition switch and the gas pedal. In 1992, his lab identified that confirmatory signal, a protein called CD28 on the T-cell surface.
Allison extended his research in the mid-1980s while at the University of California, Berkeley, where he, along with Jeff Bluestone, then at the University of Chicago, discovered that another T-cell receptor (CTLA-4) had an unexpected function; it actually stops the T-cell immune response. This landmark finding revealed that a stop signal is a critical checkpoint in the process: after the immune system is activated, CTLA-4 appears a few days later to inhibit the activation of the T cells. If cancer cells were still around at this time, they could become virtually invisible to the T cells.
These discoveries inspired in Allison the dream that manipulating signaling pathways could one day cure cancer. Cancer cells routinely arise in the human body, but most are neutralized before they turn into tumors. Allison theorized that a medication that blocks CTLA-4 from ‘putting on the brakes’, allowing the immune system to continue working, could successfully fight tumors that are able to evade the initial response. It was an incredible theory: scientists had been searching for a cure for cancer for decades and even the best medications available were highly toxic to patients. Allison’s idea of an “immune checkpoint blockade” could change the field forever.
To prove his theory, Allison developed a molecule that uniquely and specifically bound to CTLA-4, blocking its function. Pre-clinical trials of this drug in mice demonstrated that tumors could be effectively eliminated by the immune system. Allison’s groundbreaking research directly led to the development of ipilimumab, the first therapy ever to demonstrate improved overall survival in a randomized clinical trial in patients with metastatic melanoma. Ipilimumab was an unprecedented success, curing several common cancers even at end stages.
Allison’s work broke ground for the rapid advancement of novel immunotherapeutic drugs. New therapies continue to extend Allison’s work to target other immune system “braking” molecules and are now being used to successfully treat melanoma, non-small cell lung cancers, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin’s lymphoma. Allison’s innovative discoveries and their successful translation into new therapies have saved the lives of countless patients with advanced cancers.
Perhaps Allison’s disposition makes him an ideal scientist. He’s unafraid to fail. David Raulet, a former colleague of Allison’s at UC Berkeley, has commented that Allison always “had a steady eye towards how to apply fundamental knowledge for treating diseases and was quick to strike when such opportunities arose.” This description is apt as it is unexpected: Allison is mellow. Now back in Texas, he plays harmonica and still gets star struck by country music legend Willie Nelson, even though he has soloed with him in front of tens of thousands of fans at the Austin City Limits music festival.
Allison is the recipient of numerous awards, including the Nobel Prize in Physiology or Medicine (2018), the King Faisal International Prize (2018), the Wolf Prize (2017), the Balzan Prize (2017), and the Lasker-DeBakey Clinical Medical Research Award (2015). He is widely recognized for transforming contemporary thinking about cancer and its interaction with the immune system and for inspiring a paradigm shift in the treatment of patients with debilitating and fatal disease. Jim Allison’s work has truly marked the dawn of a new era in cancer treatment.
Information as of March 2019