Oct 01, 2018
On October 1, two investigators, James P. Allison, PhD, and Tasuku Honjo, MD, PhD, were honored with the 2018 Nobel Prize in Physiology or Medicine for discoveries in immunotherapy for cancer. “For more than 100 years scientists attempted to engage the immune system in the fight against cancer. Until the seminal discoveries by the two laureates, progress into clinical development was modest. Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed,” according to a press statement.
“We congratulate Drs. Allison and Honjo for leading the way towards new therapies that have already transformed the lives of countless patients while providing new hope for millions to come,” said ASCO CEO Clifford A. Hudis, MD, FACP, FASCO.
Dr. Allison, an ASCO member, was recognized for his groundbreaking investigations into the T-cell protein CTLA-4.
His story is a story of firsts, the hallmark of extraordinary discovery: Dr. Allison’s laboratory at the University of California, Berkeley, was the first to identify the structure of the T-cell antigen receptor and the first to establish CD28 as the major co-stimulatory molecule that fully activates naive T cells and prevents anergy in T-cell clones. After learning that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocks CD28-mediated co-stimulation, his laboratory was the first to show that blocking CTLA-4 with antibodies boosts T-cell responses and tumor rejection in mice. The culmination of this research was ipilimumab, a human antibody to CTLA-4, the first immune checkpoint blockade therapy approved by the U.S. Food and Drug Administration (FDA).
The road from the preclinical experiments to FDA approval was long and occasionally frustrating. Treating the immune system instead of killing cancer cells was a new approach often met with skepticism. Despite little interest from the pharmaceutical industry—initiation of the first phase I study of ipilimumab took 5 years—Dr. Allison continued his efforts to develop the strategy into a therapy for humans. Promising results soon emerged from several groups, and in 2010 an important clinical study showed striking effects in patients with advanced melanoma. In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group.
Dr. Allison is the chair of the Department of Immunology, the Vivian L. Smith Distinguished Chair in Immunology, director of the Parker Institute for Cancer Research, and the executive director of the Immunotherapy Platform at MD Anderson Cancer Center. In 2015, Dr. Allison was honored with the ASCO’s Science of Oncology Award and Lecture in 2015 for his contributions to the understanding of cancer. He has served on ASCO’s Research Methodologies in Immunotherapy Development Working Group.
Dr. Allison shares the prize with Dr. Honjo, of Kyoto University, for his separately conducted, equally incredible work in the discovery of PD-1. In animal experiments, PD-1 blockade was also shown to be a promising strategy in the fight against cancer, as demonstrated by Dr. Honjo’s laboratory and other groups. Clinical development ensued, and in 2012 a key study demonstrated clear efficacy in the treatment of patients with different types of cancer. Results were dramatic, leading to long-term remission and possible cure in several patients with previously untreatable metastatic cancer.
Dr. Honjo is a Distinguished Professor at the Kyoto University Institute for Advanced Study, a professor in the Department of Immunology and Genomic Medicine at Kyoto University, and chair of the Board of Directors of the Foundation for Biomedical Research and Innovation.
ASCO congratulates Dr. Allison and Dr. Honjo on the well-deserved recognition as Nobel laureates. Their brilliant discoveries and their tireless work have transformed that landscape of cancer care, bringing new hope to patients and their families.