AsianScientist (Oct. 1, 2018) – Professor Tasuku Honjo has been awarded the 2018 Nobel Prize in Physiology or Medicine for his discovery of the programmed cell death protein 1 (PD-1), a key player in tumor immunology. He shares the award with Professor James P. Allison, who pioneered research on the immune checkpoint protein CTLA-4, another major pathway allowing cancer cells to evade the immune system.
Cancer kills millions of people every year and is one of humanity’s greatest health challenges. 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.
Born in 1942 in Kyoto, Japan, Honjo obtained his medical degree in 1966 and received his PhD from Kyoto University in 1975. He took up faculty positions at Tokyo University and Osaka University before moving to Kyoto University where he performed his career-defining work.
In 1992, Honjo discovered PD-1, a protein expressed on the surface of a subset of immune cells known as T-cells. T-cells are involved in the immune surveillance of cancer, actively seeking out and destroying cancer cells in the body. Determined to unravel the role of PD-1, Honjo explored its function in a series of experiments in his laboratory at Kyoto University.
He showed that PD-1 functions as a brake on T-cell function. Cancer cells produce molecules that bind to PD-1 and cause T-cells to self-destruct, thereby allowing the cancer cells to evade the immune system and survive inside the body. By blocking PD-1 in animal models of cancer, Honjo was able to restore T-cell targeting of cancer cells.
His findings paved the way for the use of PD-1 inhibitors as cancer treatment in human patients. Clinical development ensued, and in 2012 a key study demonstrated clear efficacy in the treatment of patients with different types of cancer, with patients experiencing long-term remission. Several patients with metastatic cancer, a condition that had previously been considered essentially untreatable, also saw their condition improve through PD-1 inhibition.
In parallel, Allison was working on another brake on T-cells, CTLA-4. He developed an antibody that could block CTLA-4 activity, effectively removing the brakes and restoring T-cell function. In 1994, his lab demonstrated in experiments with tumor-bearing mice that the antibodies against CTLA-4 unleashed the immune system against the tumor. Further studies confirmed the efficacy of the treatment in humans.
Together, Honjo and Allison 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 the fight against cancer.
Source: The Nobel Prize Foundation; Photo: Tasuku Honjo/Kyoto University.
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