Two cancer researchers have been awarded the 2018 Nobel Prize in Physiology or Medicine for their discovery of how the immune system can be harnessed to attack tumor cells, which led to immune checkpoint inhibitor therapy.
Sharing the prestigious award are James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and Tasuku Honjo, MD, PhD, of Kyoto University in Japan.
The Nobel Assembly at Karolinska Institutet has today awarded the 2018 Nobel Prize in Physiology or Medicine jointly to James P. Allison and Tasuku Honjo.
"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," the Nobel organization said in a statement.
The Birth of Cancer Immunotherapy
During the 1990s, in his laboratory at the University of California, Berkeley, Allison was one of several scientists who discovered that the protein CTLA-4 functions as a brake on T cells. Other research teams exploited the mechanism as a target to treat autoimmune disease. But Allison had other ideas.
Having developed an antibody that binds to CTLA-4 and blocks its function, he began investigating whether CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. Allison's team performed the first experiments at the end of 1994, and the results were "spectacular," the Nobel organization said. Mice with cancer were cured with an anti-CTLA-4 agent.
Promising clinical results soon followed from several groups, and in 2010, a key clinical trial 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," the Nobel organization said.
In 1992, Honjo discovered programmed cell death 1 (PD-1), another protein expressed on the surface of T cells. In a series of experiments, Honjo showed that PD-1 (like CTLA-4) also functions as a T-cell brake, but operates by a different mechanism.
In 2012, a pivotal 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 metastatic cancer, a condition that had previously been considered essentially untreatable," the Nobel organization said.
The pioneering work of Allison and Honjo on immune checkpoint inhibitor therapy led to the development of several drugs, including ipilimumab (Yervoy, Bristol-Myers Squibb), the first of the checkpoint inhibitors, and the PD-1 inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co).
A large number of checkpoint therapy trials are currently underway against most types of cancer, and new checkpoint proteins are being tested as targets.
In 2013, cancer immunology was selected as the breakthrough of the year by the editors of Science, the flagship journal of the American Association for the Advancement of Science, as reported by Medscape Medical News.