The Nobel Prize in medicine was awarded to James Allison of MD Anderson Cancer Center and Tasuku Honjo of Kyoto University “for their discovery of cancer therapy by inhibition of negative immune regulation,” the Nobel committee announced on Monday in Stockholm.
It was a rare award for a key cancer breakthrough, in this case the discovery that the immune system can be tweaked to unleash the immune system’s tumor-attacking T cells.
The two scientists will share the 9 million Swedish kronor ($1.01 million) that comes with the prize.
The Nobel committee managed to reach Honjo by phone, but they did not have Allison’s cell number. He is in New York City for a cancer immunology conference, and got the news from his son, an architect in New York City who was watching the webcast of the Nobel announcement. Within an hour, colleagues were at his hotel room door, bearing champagne.
“I’m still in sort of a state of shock,” Allison, 70, said at a news conference shortly after the announcement. “The reason I’m really thrilled is that I’m a basic scientist. I didn’t start these studies to cure cancer, but to show how T cells work. I’m just lucky enough that, 20 years later, it’s helping cancer patients.”
Allison studied a protein on T cells called CTLA-4 that acts as a brake on the immune system. Other scientists worked on using CTLA-4 as a way to treat autoimmune disorders. Driven only by curiosity about immune cells, he had a crazy thought: Maybe CTLA-4 can be exploited to fight cancer. (His mother died of lymphoma when Allison was 10.)
By releasing the brake via an antibody that binds to and thus disables CTLA-4, he discovered in the 1990s, it was possible to unleash immune cells to swarm and kill tumors. In a key mouse experiment around Christmas 1994, Allison found that when mice with cancer were treated with CTLA-4-blocking antibodies, they were cured.
Despite little initial interest from the pharmaceutical industry, that antibody became ipilimumab, which in 2011 was approved by the Food and Drug Administration to treat metastatic melanoma. It was a breakthrough drug that turned an invariably fatal cancer that killed patients within months into one that could be cured, albeit in only a minority (about 20 percent) of patients.
In a statement to reporters after learning of his award, Allison said he was “honored and humbled.” For many scientists, he said, a driving motivation “is simply to push the frontiers of knowledge. I didn’t set out to study cancer, but to understand the biology of T cells, these incredible cells that travel our bodies and work to protect us.”
In 1992, Honjo, now 76, discovered a protein on immune cells called PD-1. It, too, operates as a T-cell brake, but via a different molecular mechanism than CTLA-4. The first anti-PD-1 drugs were pembrolizumab (Merck’s Keytruda), and nivolumab (Bristol-Myers Sqibb’s Opdivo), both initially approved in 2014 for the treatment of melanoma: Both block the PD-1 (programmed cell death 1) protein on the surface of the immune system T cells, with the result that those cells attack and, sometimes, eliminate the tumor.
The anti-PD-1 “checkpoint inhibitors” have proved even more effective than anti-CTLA-4 treatment, giving hope to patients with lung cancer, renal cancer, lymphoma, and melanoma, among others. In ongoing research, scientists are finding that combination therapy targeting both CTLA-4 and PD-1 can be even more effective, the Nobel citation noted.
The seminal discoveries represent a “paradigmatic shift in the fight against cancer,” the Nobel committee said, since they do so not by targeting the tumor cells but by tweaking the immune system.
“The power of the approach is that it allows a patient’s immune system to be unleashed to attack cancer cells based on controlled regulation through the use of drugs, specific antibodies, that target regulatory molecules on the surfaces of immune cells,” said Jeremy Berg, editor-in-chief of the Science family of journals. “The number of different types of cancers for which this immunotherapy is being found to be effective in at least some patients continues to grow.”
Indeed, there are now five marketed immunotherapies for cancer, including for lung cancer, kidney cancer, and colorectal cancer. The most recent, from Regeneron, was approved only last week.
Formally called the Nobel Prize in physiology or medicine, it is selected by the six-member Nobel Committee, the working body that solicits nominations from some 3,000 eminent researchers (including past winners) and reviews them for the 50-member Nobel Assembly at Sweden’s Karolinska Institute.
I would like to thank these two men for the part they played in saving my life.
Many people and facilities were involved.
Without Keytruda, I would not be here today.
Than you God for blessing us with these two wonderful people.
My dad has finished all the tests and is going to Moffitt next week to begin this treatment. It sounds so promising, really praying that it works for him. Kind of our last option at this point but so grateful to have it as an option at all.
Keep me in touch
It is said that President Carter was treated by this medicine. It was one of his treatments and not the only treatment. So we really do not know what cured him. I am sure there were many other people who were not cured by this medicine. How would you explain why placebo medicine cures so many diseases, including cancers? What would you say to justify that medicine effect is not same as placebo effect?
There are multiple randomized prospective placebo controlled studies that showed benefit from these medications. And yes it works on a certain percentage of patients with varying degrees. But some of them are being cured even after having metastasis and spread. The question is as Dr. Allison said Not why don’t all of these patients respond but the question is how to increase the percentage of patients responding and to try to find different ways to do so. The answer is they do work and they are very promising I promise you
Comments are closed.