Trying everything they could in mice to tweak the immune system, Krummel and Allison soon found that a protein receptor called CTLA-4 seemed to be holding T cells back, like a brake in a vehicle. Allison and Honjo set the stage in the 1990s for the current immuno-oncology boom by discovering the cancer-killing potential of CTLA-4 and PD-1, respectively. Honjo's research led to the clinical development of treating cancer patients by targeting that protein.
In 1992, Japanese scientist, Tasuku Honjo from Kyoto University, separately discovered another protein on immune cells called PD-1 and revealed that it also operates as a brake, but with a different mechanism of action to CTLA-4.
The institute added that therapies based on Prof Honjo's discovery "proved to be strikingly effective in the fight against cancer". The peace prize will be announced on Friday, and the economics prize will wrap up the Nobel season next Monday. Other scientists worked on using CTLA-4 as a way to treat autoimmune disorders. In 2000, the researchers described PD-L1, programmed death-ligand 1, a protein found on normal cell and cancer cells that binds to PD-1, and a year later, the team reported a second molecule that binds to PD-1, PD-L2.
Their breakthroughs take advantage of the immune system's ability to attack cancer cells by releasing the brakes on immune cells.
Antibodies against PD-1 have been approved by the US Food and Drug Administration as an investigational new drug for the treatment of cancer. "A succession of graduate students, postdoctoral fellows and colleagues at MD Anderson, the University of California, Berkeley, and Memorial Sloan Kettering Cancer Center played important roles in this research".
"I'm honored and humbled to receive this prestigious recognition", Allison says in a statement.
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Allison, 70, is now chair of the department of immunology at MD Anderson Cancer Center in Houston. This led him to wonder whether the immune system could provide a means to combat cancer and strengthened his belief that it could provide a much more effective and less toxic form of therapy than radiation and chemotherapy, the devastating effects of which he had witnessed in both his mother and uncle. Allison, initially driven only by curiosity about immune cells, had a insane thought: Maybe CTLA-4 can be exploited to fight cancer. He announced about a year later that he no longer needed treatment. "And I thought, 'If we could do that in people, this is going to be incredible'".
"Targeted therapies don't cure cancer, but immunotherapy is curative, which is why many consider it the biggest advance in a generation", Allison said in a 2015 interview.
Allison started his career at MD Anderson in 1977, arriving as one of the first employees of a new basic science research center located in Smithville, Texas.
The duo will share the Nobel prize sum of nine million Swedish kronor (about $1.01 million or 870,000 euros).
Medicine is the first of the Nobel Prizes to be handed out each year.