Prof. James Allison First Gets 'Israeli Nobel,' then Sweden’s Nobel

Great are the works of the Lord, studied by all who delight in them. (Psalm 111:2)

What do you do if you want a good chance to win a Nobel Prize in the sciences? Just pray that you first receive a Wolf Prize, which is considered “Israel’s Nobel.” This prize for academic excellence is an incredible predictor of future Nobel distinction.

Almost a third of Nobel laureates in the sciences were first awarded the Wolf Prize, an international award – granted in Jerusalem – that has been presented most years since 1978 to living scientists and artists for “achievements in the interest of mankind and friendly relations among people … irrespective of nationality, race, color, religion, sex or political views.” The categories are agriculture, chemistry, mathematics, medicine, physics as well as the arts.

The latest Nobel laureate to prove the rule is to Prof. James P. Allison of the US, who will share his award in Physiology and Medicine with Prof. Tasuku Honjo of Japan. Last year, Allison came to Jerusalem to receive his Wolf Prize. Fourteen of the 26 winners of the Wolf Prize in physics between 1978 and 2010, for example, have gone on to win the Nobel Prize in that field, five of them in the following year. The Technion-Israel Institute of Technology’s Prof. Dan Schectman, who won the Nobel for chemistry in 2011, followed that pattern by winning a Wolf Prize the year before.

The Nobel Assembly at Karolinska Institute – one of the world’s foremost medical universities and Sweden’s single-largest center of medical academic research – decided this year to reward the achievements of the two for their discovery of cancer therapy by inhibition of negative immune regulation.

Cancer kills millions of people every year and is one of humanity’s greatest health challenges, said the Assembly. “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 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, 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 the discovery, the Swedes continued, 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.”

Cancer is not one disease but many different disorders, each of them involving the uncontrolled proliferation of abnormal cells that have the capacity for spread to healthy organs and tissues. A number of therapeutic approaches are available for cancer treatment, including surgery, radiation, and other strategies, some of which have been awarded previous Nobel Prizes.

Among the previous discoveries in the war against cancer were hormone treatment for prostate cancer (Huggins, 1966), chemotherapy (Elion and Hitchins, 1988), and bone-marrow transplantation for leukemia (Thomas 1990). But, continued the Assembly, advanced cancer remains immensely difficult to treat, and novel therapeutic strategies are desperately needed.

In the late 19th century and beginning of the 20th, some researchers though that activation of the immune system might be a strategy for attacking tumor cells. They tried to infect patients with bacteria to activate the defense, but these efforts only had modest results. A variant of this strategy is used today in the treatment of bladder cancer.
So much more had to be learned. Many scientists conducted intense basic research and uncovered fundamental mechanisms regulating immunity and how the immune system can recognize cancer cells. Despite remarkable scientific progress, attempts to develop generalizable new strategies against cancer proved difficult.

The immune system’s main characteristic is its ability to discriminate “self” from “nonself” so that invading bacteria, viruses and other dangers can be attacked and eliminated. T cells, a type of white blood cell, are key players in this defense and were shown to have receptors that bind to structures recognized as non-self and such interactions trigger the immune system to engage in defense. But additional proteins acting as T-cell accelerators are also required to trigger a full-blown immune response.

During the 1990s, in his laboratory at the University of California at Berkeley, Allison studied the T-cell protein CTLA-4. He was one of several scientists who noticed that CTLA-4 functions as a brake on T cells and 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 Now he aimed at investigating if CTLA-4 blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells. He and his team performed a first experiment at the end of 1994, with spectacular results. Mice with cancer had been cured by treatment with the antibodies that inhibit the brake and unlock antitumor T-cell activity. His and other teams then worked on humans. Eight years ago, an important clinical study showed striking effects in patients with advanced melanoma, a potentially deadly type of skin cancer.
Checkpoint therapy has now revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed, the Assembly concluded.

Allison, then chairman of the immunology department at the MD Anderson Cancer Center at the University of Texas, received his Wolf Prize for Medicine in 2017.

The Wolf Foundation began its activities 42 years ago with an initial endowment fund of $10 million founded by Dr Ricardo Wolf, a German-born inventor and former Cuban ambassador to Israel. Since its inception, the foundation has awarded more than 300 prizes, and nearly two dozen Israelis have been among the winners. Most of the laureates are from the US, followed by the UK.

The Wolf Prize in Medicine is probably the third most prestigious, after the Nobel Prize and the Lasker Award, in this field.

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