A series of scientific advances over the last century made cancer a less deadly disease. This year’s Nobel Prize in medicine was awarded to two scientists for one such advancement.
The 2018 Nobel Prize in physiology or medicine has gone to James Allison from the University of Texas and Tasuku Honjo from Kyoto University. Independently, both scientists discovered how cancer can be treated by targeting the immune system.
What did they do?
Our immune system protects us from disease, but it has built-in safeguards to stop it from attacking our own tissue. The idea of mobilizing the immune system to tackle cancer was first proposed more than a century ago, but it was only after the discoveries of Allison and Honjo that this tantalizing possibility could be turned into a clinical treatment.
Allison and Honjo discovered a way to unleash our immune cells against cancer by turning off the proteins that put the brakes on. And that has led to the development of new drugs, which now offer hope to patients with advanced and previously untreatable cancer.
How did they do it?
In the 1990s, Allison, who was at the University of California at Berkeley, was studying a receptor called CTLA-4, which acts to slow down the activity of T cells. Drugs meant to enhance the CTLA-4 receptor were already being studied to treat people with overactive immune systems. Allison wondered what would happen if, instead of enhancing the receptor, scientists tried to block its activity. Turns out, that would cause T cells to become more active and attack cancer cells.
At about the same time, across the Pacific Ocean, Honjo at Kyoto University in Japan was studying a different T cell brake receptor, called PD-1. Blocking PD-1 had a similar effect, causing T cells to attack cancer. Better still, PD-1 seemed to be able to achieve the feat for a wider range of cancers.
How much time did the discovery take?
After nearly 20 years of work, clinical trials in the 2010s began to prove Allison and Honjo right. PD-1 therapy is being shown to be effective against lung, breast, and skin cancer, as well as lymphoma, or the cancer of the immune system. Better still, combination therapies of blocking CTLA-4 and PD-1 are even more effective in patients with melanoma.
Why is this therapy game changing?
The head of the Genome Engineering Lab at MIPT, Pavel Volchkov, explains why the discoveries of the checkpoint molecules have transformed the paradigm of fighting cancer: “This pioneering work induced a new wave of research, which led to multiple clinical cancer therapies. The whole world has come to recognize the fact that the immune system is the most functional, most powerful means of fighting cancer. In a recent Nature Medicine paper of June 2018, scientists described a case of breast cancer that was successfully treated. And that wouldn’t ever happen without the fundamental work by Allison and Honjo.”
Today, such cancer treatments are called checkpoint therapies. As with other cancer therapies, there are side effects, as T cells sometimes attack healthy cells, too. But the side effects are usually manageable, and researchers are looking for ways to reduce them. The Nobel committee says that Allison and Honjo’s work amounted to a “landmark in our fight against cancer.”
What makes this discovery unique?
Raymond Stevens, a professor of molecular biology and chemistry at the Scripps Research Institute in La Jolla, California, who is now attending the Biomembranes conference at MIPT, and who worked with Allison back at the University of California, Berkeley, embraced the decision of the prize committee.
“One of the challenges in science today is that everybody works in their individual fields, but very seldom two fields work together,” Stevens said. “This time it was immunology and oncology teaching the immune system how to help fight cancer. That goes against what most people had been thinking and so my hope is that this is going to stimulate people to think, ‘Oh, we can mix fields together and make big discoveries!’”