Nobel Prize Goes to Cancer Immunotherapy Pioneers

By Megan Brooks
WebMD Health News

Oct. 1, 2018 -- Two cancer researchers received the 2018 Nobel Prize in Physiology or Medicine for discovering how the immune system can be harnessed to attack tumor cells, a finding that led to the development of immunotherapy drugs.

Sharing the prestigious award are James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and Tasuku Honjo, MD, PhD, of Kyoto University in Japan.

"For more than 100 years scientists attempted to engage the immune system in the fight against cancer," the Nobel organization said in a statement. The "therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed."

During the 1990s, in his laboratory at the University of California, Berkeley, Allison was one of several scientists who discovered that the protein CTLA-4 works as a brake on a type of immune cell known as T cells.

He developed an antibody that blocked the way it worked, then began investigating whether that blockade could free the T-cell brake and unleash the immune system to attack cancer cells. Allison's team did the first experiments at the end of 1994, and the results were "spectacular," the Nobel organization said. Mice with cancer were cured with an anti-CTLA-4 agent.

Promising results soon followed from several groups, and in 2010, a key test showed striking effects in patients with advanced melanoma. "In several patients signs of remaining cancer disappeared. Such remarkable results had never been seen before in this patient group," the Nobel organization said.

In 1992, Honjo discovered PD-1, another protein on the surface of T cells. In a series of experiments, Honjo showed that PD-1 also works as a T-cell brake, but operates in a different way.

In 2012, a pivotal study demonstrated clear results for patients with different types of cancer. "Results were dramatic, leading to long-term remission and possible cure in several patients with metastatic cancer, a condition that had previously been considered essentially untreatable," the Nobel organization said.

The pioneering work of Allison and Honjo led to the development of several drugs, including ipilimumab (Yervoy), the first immunotherapy drug, and the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda).

A large number of trials for the drugs -- also known as checkpoint inhibitors -- are underway against most types of cancer, and new proteins are being tested as targets.

In 2013, cancer immunology was selected as the breakthrough of the year by the editors of Science, the flagship journal of the American Association for the Advancement of Science.



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