[Updated, 11:45 am ET, with comments from press conference] Harnessing the immune system to fight cancer has transformed the treatment of many cancers, and the lives of countless cancer patients who have seen their disease go into remission. This has led many people to speculate over the last several years that the founding researchers of the cancer immunotherapy field would win the Nobel Prize in Physiology or Medicine. Today, that prediction came true.
James Allison of MD Anderson Cancer Center and Tasuku Honjo of Kyoto University in Japan were awarded the prestigious prize, for their discovery of immune “checkpoints,” key proteins on T cells that dampen immune responses, and for work showing that blocking these proteins could unleash the immune system on tumors.
Allison, while working at the University of California, Berkeley, in the 1990s, was studying a T cell protein called CTLA-4 and had come up with an antibody that could bind and inhibit CTLA-4. With this antibody, he and his team essentially cured tumor-ridden mice of their cancers in initial experiments in the mid-1990s.
Allison struggled to attract interest from pharma companies at the time but eventually found collaborators at a small company called Medarex, which developed an anti-CTLA-4 antibody that would soon be called ipilimumab. Bristol-Myers Squibb (NYSE: BMY) acquired Medarex in 2009 for $2.4 billion, and ipilimumab (Yervoy) went on to become the first checkpoint inhibitor approved by the FDA, in 2011. Yervoy, approved as a single agent for melanoma (and in combination with another checkpoint inhibitor for other cancers), brought in $1.2 billion in global revenue for Bristol in 2017.
Tasuku Honjo discovered the T cell protein, PD-1, in 1992, and found that it acts like a brake on T cell activity. He and other research groups showed similar promising results as Allison did when they inhibited PD-1 with antibodies in mice with cancer.
The first PD-1 inhibitors, nivolumab (Opdivo) from Bristol and pembrolizumab (Keytruda) from Merck (NYSE: MRK), were approved by the FDA in 2014, and are used to treat skin, lung, and other cancers. Nivolumab, Bristol’s top-selling drug in 2017, earned the company $5 billion in global revenue that year, and pembrolizumab brought in $3.8 billion for Merck the same year.
The work of Allison and Honjo helped launched the huge immuno-oncology field of drug development that today includes numerous biotechs, not to mention most, if not all, major pharma and large biotech companies. The crowded global market for checkpoint inhibitors is projected to grow to $30 to $35 billion in the next decade, and more than 1,000 clinical trials are underway testing these drugs in various combinations.
In a press conference today, Allison said he was still in shock about the news (he found out early this morning from his son who watched the Nobel webcast), and expressed optimism about the future of the field. “Immunotherapy is going to be part of therapy that potentially all cancer patients will receive in five years,” said Allison. “It’s going to be curative in a lot of these patients.”