The 2018 Nobel Prize for Physiology or Medicine has been awarded to James Allison from the University of Texas MD Anderson Cancer Centre and Tasuku Honjo from Kyoto University for their work on harnessing the body’s immune system to attack cancerous tissue. Their work, which was done in parallel, revealed that it is possible to turn off the ‘brakes’ preventing the immune system from attacking cancerous cells, a technique which has subsequently been used as the basis for cancer immunotherapy. Through these treatments, a number of patients with otherwise untreatable conditions have seen their tumours shrink drastically.

“James Allison studied a known protein that functions as a brake on the immune system,” the Nobel Assembly at the Karolinksa Institutet in Sweden said in their announcement yesterday. “He realised the potential of releasing the brake and thereby unleashing our immune cells to attack tumours. 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 prove to be strikingly effective in the fight against cancer.”

Specifically, Dr Allison was investigating a T cell surface receptor called cytotoxic T-lymphocyte antigen 4 (CTLA-4), which was discovered by French immunologists in the ‘80s. Through his work, Dr Allison (and others) found that the receptor was acting as a brake that prevented the T cells, a major component of the human immune system, from triggering a full immune response. While many groups were interested in the receptor for its potential in treating autoimmune conditions, Dr Allison wanted to find out whether or not inhibiting it would enable the immune system to target cancerous tissue that otherwise went undetected.

In 1996, Dr Allison and his team published a paper in Science that revealed inhibition of CTLA-4 had successfully reduced tumour size in mice.

At roughly the same time, Dr Honjo discovered a molecule that was expressed in dying T cells that he named programmed death 1 (PD-1) and identified as another immune response brake. At the time, he didn’t realise there was a possible connection between PD-1 and cancer, but later work by Dr Honjo and others revealed that the molecule was even more effective in immunotherapy than CTLA-4.

The first drug based on this type of cancer treatment was approved in 2011, and the long-term effects of immunotherapy have so far been promising.

“I want to continue this research so that in the future, this therapy will contribute to curing as many patients as possible,” said Dr Honjo yesterday from Kyoto. “We need to determine why this immune therapy does not work in certain cases.

“I believe this disease will be cured by the end of this century.”