James P. Allison, Ph.D., director of the Cancer Research Institute Scientific Advisory Council, has been awarded the 2018 Nobel Prize in Physiology or Medicine. Having already received the Lasker-DeBakey Clinical Medical Research Award—also known as the “American Nobel”—in 2015, the “Texas T Cell Mechanic” can now add the more renowned international version to his resume. Along with Dr. Allison, Tasuku Honjo, M.D., Ph.D., of Kyoto University School of Medicine is also a recipient of this Nobel Prize.
Dr. Allison—who currently serves as the Vivian L. Smith Distinguished Chair in Immunology and the executive director of the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center—was chosen for this year’s Nobel Prize for his groundbreaking work that helped to propel the field of cancer immunotherapy, which has revolutionized cancer treatment over the past decade. Following Science’s announcement of immunotherapy as the Breakthrough of the Year in 2013 and the American Society of Clinical Oncology naming it the Clinical Advance of the Year in 2016, 2017, and 2018, this Nobel Prize represents the latest validation of the fruits borne by immunotherapy’s progress over the past few decades.
Dr. Allison’s most important contributions involved his work on the CTLA-4 immune checkpoint receptor. After helping to show that CTLA-4 functions as a “brake” on T cells and prevents them from exerting their disease-fighting ability, he was the first to demonstrate that blocking CTLA-4 with an antibody could prevent tumor development in mice as well as enable them to eliminate large, established tumors.
But he refused to allow the potential benefits of this approach to remain confined to the lab.
Motivated by his personal encounters with cancer—he lost his mother, two uncles, and later a brother to cancer—Dr. Allison fought passionately to translate his findings into medicine for human patients, which led to the development of a humanized anti-CTLA-4 antibody, now known as ipilimumab. In 2010, ipilimumab became the first treatment—of any type—to improve survival in metastatic melanoma patients, and in 2011 it became the first FDA-approved checkpoint immunotherapy, which marked a turning point in immunotherapy and “created a whole new approach … one that is radically improving—and in many cases saving—the lives of people with cancer,” according to Jill O’Donnell-Tormey, Ph.D., Cancer Research Institute CEO and director of scientific affairs.
Since ipilimumab’s development, it has been used to treat tens of thousands of patients with advanced melanoma, almost 20% of whom have remained alive a decade after treatment—an almost unheard of success rate in a cancer which claims the lives of nearly half of patients within a year. These long-term benefits appear to be due, in part, to ipilimumab’s ability to generate immune memory via long-lived immune cells that can protect patients if their cancer cells return later. Though immunotherapy’s clinical value is now widely accepted, at the time Dr. Allison had to persistently plead to convince people to invest in this immune-based approach, which was still considered a risky idea at the fringe of mainstream medicine.
Ipilimumab’s clinical successes paved the way for the next wave of immunotherapies, which targeted the PD-1/PD-L1 checkpoint pathway. This is where Tasuku Honjo, M.D., Ph.D., of Kyoto University School of Medicine—also a recipient of the 2014 William B. Coley Award—made his mark. Five of these checkpoint immunotherapies have now been approved by the FDA for various cancers, including one that became the first and only cancer treatment of any type to be approved for tumors with a certain genetic biomarker, “regardless of their origin.”
Prior to his breakthroughs involving CTLA-4, Dr. Allison was also one of the first to identify the T cell receptor protein in the early 1980s. Later, he demonstrated that the co-stimulatory CD28 receptor, which acts as a “gas pedal” on T cells, is required for their activity.
Now, Dr. Allison's focus is on improving the effectiveness of immunotherapy for even more patients. To do so, he and his colleagues are exploring combination approaches that utilize immunotherapies, including personalized cancers vaccines, in ways designed to most effectively stimulate immune responses against patients’ tumors. To that end, he currently co-leads the CRI-SU2C Dream Team, which is investigating checkpoint and cell-based immunotherapies. Additionally, he serves as a sponsor of current CRI postdoctoral fellow Stephen Mok, Ph.D., and has also sponsored several former CRI postdoctoral fellows.
Although he originally “just wanted to see how the immune system works” and never planned to go into cancer research, Dr. Allison’s path lends credence to his belief that a biomedical scientist’s most important job should be to “ask important questions in fundamental biology and every now and then think about how this impacts human health, rather than spend all your time trying to solve a health issue.”
In his spare time, Dr. Allison is an avid harmonica player and frequently rocks out with fellow immunologists in a garage band they formed called “The Checkpoints.” He’s even played on stage alongside country music legend Willie Nelson.
In addition to receiving the Nobel Prize and the Lasker-DeBakey Award, Dr. Allison has received many other accolades, including the 2005 William B. Coley Award, the inaugural CRI-AACR Lloyd J. Old Award in 2013 (named after the “Father of Modern Tumor Immunology,” whom Allison succeeded as the director of CRI’s Scientific Advisory Council), and the 2014 Szent-Györgyi Prize. He was also chosen for Time's 100 Most Influential People and is a member of the National Academy of Sciences and the Institute of Medicine as well as a Fellow of the AACR Academy.
From all of us here at the Cancer Research Institute, we wish to extend our sincere gratitude for all that you’ve done to advance the field of cancer immunotherapy and to save the lives of patients. Congratulations on this great honor Dr. Allison and Dr. Tasuku Honjo!