Cancer immunologists scoop medicine Nobel prize James Allison and Tasuku Honjo pioneered treatments that unleash the body’s own immune system to attack cancer cells.

Two scientists who pioneered an entirely new way to treat cancer have won the 2018 Nobel Prize in Physiology or Medicine. James Allison at the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo at Kyoto University in Japan will share the 9 million Swedish kronor (US$1 million) prize. The pair showed how proteins on immune cells can be used to manipulate the immune system so that it attacks cancer cells. The approach has since led to the development of therapies that have been hailed for extending survival in some people with cancer by years, and even wiped out all signs of disease in some people with advanced cancers. Researchers have flocked to the approach, and immunotherapy is now one of the hottest areas in cancer research. Early excitement Allison is in New York for an immunology conference, and was awoken at 5.30 by a call from his son delivering the good news. By 6.30, colleagues were banging on the door of his hotel room bearing champagne for an impromptu party. The Nobel Committee only reached him some time after that. “It still hasn’t completely dawned on me,” said Allison, at a press conference. “I was a basic scientist. To have my work really impact people is one of the best things I could think about. It’s everybody’s dream.” Tweets by the Nobel Prize showing the winners celebrating with colleagues, friends and families in their respective countries In the 1990s, Allison, then at the University of California, Berkeley, was one of several scientists who studied a ‘checkpoint’ protein, CTLA-4, that acts as a brake on immune cells called T cells. In 1997, Allison and his colleagues engineered an antibody that could bind to CTLA-4, removing the brakes on T-cell activity and unleashing them to attack cancer cells in mice. A clinical study in 2010 found that the antibody had a striking effect on people with advanced melanoma, a form of skin cancer1. Working independently of Allison, in 1992, Honjo discovered a different T-cell protein, PD-1, which also acts as a brake on the immune system but by a different mechanism. PD-1 went on to become a target in the treatment of cancer. In 2012, research in people revealed that the protein was effective against several different cancers, including lung cancer, a major killer2. The results were dramatic — some patients with metastatic cancer went into long-term remission, raising the possibility of a cure. Releasing the brakes “Allison’s and Honjo’s discoveries have added a new pillar in cancer therapy. It represents a completely new principle, because unlike previous strategies, it is not based on targeting the cancer cells, but rather the brakes — the checkpoints — of the host immune system”, said Klas Kärre, a member of the Nobel Committee and an immunologist at the Karolinska Institute in Stockholm who described the work of the prizewinners during the Nobel announcement. “The seminal discoveries by the two laureates constitutes a paradigmatic shift and a landmark in the fight against cancer.” In recent years, clinical work on drugs that inhibit the CTLA-4 and PD-1 mechanisms — known as ‘immune checkpoint therapy’ — has developed apace. Treatments that block PD-1 have been shown to be effective in lung and renal cancers, lymphomas and melanoma. Recent clinical work that combined therapies targeting CTLA-4 and PD-1 in patients with melanoma showed that this approach can be even more effective than CTLA-4 alone3. Trials are now underway to evaluate the efficacy of checkpoint therapy against most types of cancer, and scientists are testing numerous other checkpoint proteins to see if they could act as targets.