Nobel Prize Awarded in Medicine for cancer research – 2018

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Nobel Prize Awarded in Medicine for cancer research

Branch of the Prize: Medicine

Year: 2018

Winner of Nobel Prize in Medicine 2018:

1. James P. Allison

Born: 7 August 1948, Alice, TX, USA

Affiliation at the time of the award: University of Texas MD Anderson Cancer Center, Houston, TX, USA , Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA

Prize motivation: “for their discovery of cancer therapy by inhibition of negative immune regulation.”

Prize share: 1/2

2. Tasuku Honjo

Born: 27 January 1942, Kyoto, Japan

Affiliation at the time of the award: Kyoto University, Kyoto, Japan

Prize motivation: “for their discovery of cancer therapy by inhibition of negative immune regulation.”

Prize share: 1/2

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Summary of their Works:

Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.

Allison, chair of Immunology and executive director of the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center, studied a protein that functions as a brake on the immune system. Releasing the brake allowed immune cells to attack tumors, he found.
The discovery led to effective treatments, specifically some called immune checkpoint blockade therapies.
“I’m a basic scientist. I did not get into these studies to try to cure cancer. I got into them because I wanted to know how T cells work,” Allison said.
T cells, a type of white blood cell, are part of the immune system and help protect the body from infection and may help fight cancer, according to the National Cancer Institute.

Allison’s work led to development of the first immune checkpoint inhibitor drug, according to MD Anderson Cancer Center. Ipilimumab, which has the brand name Yervoy, was approved for late-stage melanoma by the US Food and Drug Administration in 2011 and became the first to extend the survival of patients with late-stage melanoma.
Now, ipilimumab is also approved to treat colorectal cancer and a type of kidney cancer called renal cell carcinoma, and is being studied in the treatment of other types of cancer.

James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand new approach for treating patients.

In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer.

Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer.

A new principle for immune therapy:

During the 1990s, in his laboratory at the University of California, Berkeley, James P. Allison studied the T-cell protein CTLA-4. He was one of several scientists who had made the observation that CTLA-4 functions as a brake on T cells. Other research teams exploited the mechanism as a target in the treatment of autoimmune disease. Allison, however, had an entirely different idea. He had already developed an antibody that could bind to CTLA-4 and block its function (see Figure). He now set out to investigate if CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. Allison and co-workers performed a first experiment at the end of 1994, and in their excitement it was immediately repeated over the Christmas break. The results were spectacular. Mice with cancer had been cured by treatment with the antibodies that inhibit the brake and unlock antitumor T-cell activity. Despite little interest from the pharmaceutical industry, Allison continued his intense efforts to develop the strategy into a therapy for humans. Promising results soon emerged from several groups, and in 2010 an important clinical study showed striking effects in patients with advanced melanoma, a type of skin cancer. In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group.

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