This year’s Nobel Prize in Medicine or Physiology has been announced and the joint winners are literal life-savers.
Dr. Jim Allison is currently the Chair of Immunology and the Executive Director of the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center. He is being recognized for work he conducted while at the University of California at Berkeley and the Memorial Sloan Kettering Cancer Center in New York.
Dr. Tasuku Honjo is being honored for work conducted at Kyoto University, where he is still a professor. He has also worked at Osaka University, the University of Tokyo, and the National Institutes of Health in Washington.
Although Dr. Honjo is a medical doctor, Dr. Allison is not. Both men have had long, successful research careers in the field of immunology. Each independently discovered ways of helping the immune system attack cancerous tumors in the 1990’s. They, and other researchers and medical doctors, then used the discoveries to develop immunotherapy drugs. It wasn’t long before at least one recipient previously considered terminal was declared cancer-free.
Immunotherapy was an old idea, even in the 1990’s, but no one had succeeded in turning the immune system against cancer, and the prospect that anyone might have had success in this approach had come to seem very dim. Dr. Honjo and Dr. Allison each found a way while researching one particular aspect of the immune system, the T-cell.
T-cells are are a class of blood cells that are part of the adaptive immune system. But excessive production of T-cells, or excessive T-cell activity, is bad for the body, so there are various mechanisms or “checkpoints” that inhibit them. Unfortunately, some types of cancer can deliberately activate those mechanisms and turn the T-cells off. Others simply take advantage of the system’s natural limitations. Dr. Honjo discovered one such mechanism, and how to block it. Dr. Allison discovered and blocked another. By blocking one or the other mechanism, the new immunotherapy treatments dramatically increase the chance that the T-cells will successfully attack the cancer.
No one treatment works on all cancers, nor do all types of cancer have their own form of immunotherapy yet. The list of cancers that can be treated with one or another of the newly-developed drugs includes melanoma, Hodgkin’s lymphoma, and cancers of the lung, kidney, bladder, liver, cervix, digestive system, head, and neck. Immunotherapies have the potential to cure at least some forms of metastatic cancer, a stage otherwise considered incurable.
Still, while immunotherapy offers hope to some who previously had none, not everyone responds to the new drugs, which can also have serious side effects. Dr. Allison acknowledges the problem, explaining that “One challenge is that the clinical success has outrun our scientific knowledge of how these drugs work and how they might best be combined with other therapies to improve treatment and reduce unwanted side effects. We need more basic science research to do that.”
Dr. Allison is continuing to work, both as a researcher and in a leadership capacity, on that needed research, developing new possibilities for cancer treatments and an increasingly better understanding of the immune system.
In a press conference after the announcement, Dr. Allison expressed shock and gratitude, thanked the students and colleagues who had assisted his research, and gave a “shout out” to current cancer patients, reminding them that more treatments are being developed. He also explained that cancer is a very personal issue for him, since several members of his family have had cancer, and his mother died of it while he was still very young.
He did not get into immunology in order to cure cancer, he explained. He was simply doing research in order to better understand how the human body works. However, he was always aware that there could be a practical application, and would often stop to review his work and consider whether anything he discovered could be applied to fighting cancer. Eventually, of course, the answer turned out to be yes.
“It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade,” Dr. Allison said. “They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”
Dr. Honjo expressed a similar sentiment, saying at his own press conference at Kyoto University, “It is really, really an honor,” and that he hopes his winning the Nobel “will give encouragement to many researchers in basic studies.”
That basic science—research conducted for the sake of knowledge, without an obvious practical objective—can become the key to a major advance in medicine is an important part of the story for both men.
Dr. Honjo, like Dr. Allison, did not set out to work on cancer. He, too, was simply curious as to the functioning of T-cells, especially the process by which the cells die. His insight was that what he called “programmed cell death” is a control mechanism or checkpoint that can be turned off. Curiously, drugs developed based on his work have milder side effects than those that use Dr. Allison’s checkpoint blockade.
Dr. Honjo, too, is now focused on further developing the potential of his work.
“I want to continue this research so that in the future, this therapy will contribute to curing as many patients as possible,” Honjo explained. “We need to determine why this immune therapy does not work in certain cases.” As regards the future of immunotherapy, he is optimistic, saying “I believe this disease will be cured by the end of this century.”
Both men are highly decorated and well-respected scientists, with the duo also sharing in the Tang Prize in 2014 for their work with T-cells. But awards are not the most important thing.
Dr. Honjo told the story of being approached by someone at his golf club.
“He told me, ‘Thanks to you I can play golf again.’ That was a blissful moment. A comment like that makes me happier than any prize.”