Bharat SainiLast Updated on October 24, 2018 by Bharat Saini
Nobel Prize for Physiology or Medicine 2018 has been won by two immunologists James P Allison of the MD Anderson Cancer Centre, USA, and Tasuku Honjo from the Kyoto University, Japan, who discovered how to harness the body’s immune system to fight cancer.
The duo will share the nine million Swedish kronor (£775,000) prize, announced by Professor Thomas Perlmann, Secretary the Nobel Committee for Physiology or Medicine, at the Karolinska Institute in Stockholm on Monday October 1, 2018.
They will receive their prize from King Carl XVI Gustaf at a formal ceremony in Stockholm on December 10, the anniversary of the 1896 death of Alfred Nobel who created the prizes in his last will and testament.
Nobel Assembly said that the pair was honoured “for their discovery of cancer therapy by inhibition of negative immune regulation”.
Allison and Honjo had in 2014 won the Tang Prize, touted as Asia’s version of the Nobel for their research.
It is the first time the development of a cancer therapy has been recognised with a Nobel Prize.
The immune system normally seeks out and destroys mutated cells, but cancer finds sophisticated ways to hide from immune attacks. One way is by ramping up braking mechanisms designed to prevent immune cells from attacking normal tissue.
Immune checkpoint inhibitor therapy targets proteins made by some immune system cells, as well as some cancer cells. The proteins can stop the body’s natural defences from killing cancer cells. The therapy is designed to remove this protein “brake” and allow the immune system to more quickly get to work fighting the cancer.
Allison discovered in the 1990s, the first of these built-in brakes, known as checkpoints. He studied a known protein that functions as a brake on the immune system. He realised the potential of releasing the brake and thereby unleashing our immune cells to attack tumours. He then developed this concept into a new approach for treating patients. In 1995, Allison was one of two scientists to identify the CTLA-4 molecule as an inhibitory receptor on T-cells. T-cells are a type of white blood cells that play a central role in the body’s natural immunity to disease.
Other teams were investigating the potential of enhancing the action of checkpoints to treat autoimmune diseases, but Allison showed that doing the reverse – switching off the brakes – could produce remarkable results in treating mice with cancer.
Honjo discovered independently in 1992 a second checkpoint, a different protein on immune cells, the ligand PD-1, that also appeared to operate as a brake, that worked through a different mechanism and treatments based on this work have produced dramatic improvements to patient outcomes in the clinic.
The idea of mobilising the immune system to tackle cancer was first proposed more than a century ago, but it was only after the discoveries of Allison and Honjo that this tantalizing possibility could be turned into a clinical treatment.
The resultant drugs, known as checkpoint inhibitors, have significant side effects but have been shown to produce remarkable results in treating lung cancer, renal cancer, lymphoma, and melanoma.
The ground breaking work of Allison and Honjo on inhibiting the immune system to combat cancer is already considered transformative as it has paved the way for a new class of cancer drugs that are already dramatically changing outcomes for patients, but will doubtless prolong many more lives as therapies based on the breakthroughs are developed further.
A large number of checkpoint therapy trials are currently underway against most types of cancer.
Honjo, who began his research after a medical school classmate died from stomach cancer, said: “I want to continue my research … so that this immune therapy will save more cancer patients than ever.”
Allison had a family history of cancer as his mother died of lymphoma when he was 10 and having witnessed the ravages of radiotherapy and chemotherapy meant he always had an eye on whether his work might lead to a new therapy, said: “I’m a basic scientist. I didn’t get into these studies to cure cancer; I wanted to understand how T cells work.” “It was always in the back of my mind”.
