The Nobel Prize in Physiology or Medicine 2018 was awarded to James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation. Cancer is the second leading cause of death globally, and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer. This discovery by Allison and Honjo has provided a revolutionary principle for research into cancer therapy.
James P. Allison
Allison studied a known protein, CTLA-4, that functions as a brake on the immune system, specifically, T cells. He realised the potential of releasing the brake and unleashing immune cells to attack tumours. Having already developed an antibody that is able to bind to CTLA-4 and block its function, he continued to research if the CTLA-4 blockade could disengage the T-cell brake and allow our immune cells to attack tumours.
Additionally, Tasuku Honjo discovered a protein expressed on the T-cells, PD-1, which also operates as a brake, but with a different mechanism of action. He discovered that PD-1 blockade was also a promising strategy in the fight against cancer. When a study was conducted in the treatment of patients with different types of cancer, using his discovery, results showed long-term remission and a possible cure in several patients with metastatic cancer, previously thought to be untreatable.
Of both Honjo and Allison’s strategies, checkpoint therapy against PD-1 has proven more effective and has shown positive results in cancers including lung cancer, renal cancer, lymphoma and melanoma. However a combining therapy which targets both CTLA-4 and PD-1 is thought to be even more effective and has inspired efforts to combine these strategies to eliminate tumour cells even more efficiently. Both these discoveries will be revolutionary to the lives of many in the treatment opportunities that future research may lead to and constitute a landmark in our fight against cancer.