James P. Allison
Wolf Prize Laureate in Medicine 2017
James P. Allison
Affiliation at the time of the award:
University of Texas MD Anderson Cancer Center, USA
“for sparking a revolution in cancer therapy through (his) discovery of immune checkpoint blockade”.
Jim Allison made major contributions to our understanding of the immune system beginning with his early work on defining the T cell receptor and continuing with his recognition that T cell activation also required engagement of costimulatory receptors. But his greatest achievement is his brilliant insight that the CTLA-4 receptor was an inhibitory, not an activating, receptor for T cells. Allison’s brilliant insight that blocking the function of inhibitory receptors on T lymphocytes could result in activation of anti-tumor immunity forever transformed the field of immunotherapy, which had languished for many years. In a seminal series of pre-clinical studies, Allison demonstrated that treatment of melanoma-bearing mice with antibody to CTLA-4 resulted in impressive tumor regressions. Despite skepticism in the field, Allison persevered in touting immune blockade of CTLA-4 as a novel form of cancer immunotherapy. This ultimately led to the development and FDA approval in 2011 of an anti-human CTLA-4 monoclonal antibody, ipilimumab, that led to durable remissions in some patients with advanced melanoma, some of whom are still alive today a decade after treatment. The discovery of immune checkpoint blockade by Allison eventually led to the FDA approval of an additional class of drugs that blocked a second inhibitory receptor, PD-1, or its ligand, PDL1. This approach, termed “checkpoint inhibition” or “checkpoint blockade” has now resulted in activation of anti-tumor immunity against many cancers. Allison’s success arose from highly innovative basic science discoveries that ultimately were translated successfully into new therapies that have saved the lives of patients with advanced cancer. The emergence of immunotherapy as a fourth pillar in cancer treatment along with surgery, radiation, and chemotherapy was hailed by Science magazine as the 2013 Breakthrough of the Year.