Cancer immunotherapy researchers awarded 2018 Nobel Prize in Medicine
The 2018 Nobel Prize in Medicine is awarded to two researchers who discovered thatthe cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) proteins limit the ability of T cells to attack cancer cells. Their discovery led to the development of immune checkpoint inhibitors that have revolutionized cancer treatment.
Dr James Allison of the University of Texas MD Anderson Cancer Center in Houston, Texas, US, discovered the CTLA-4 protein. He then developed an antibody against CTLA-4 and performed the first experiment on its antitumour activity in mice with cancer in 1994. Despite lukewarm interest from the pharmaceutical industry initially, Allison persisted in his efforts to develop the strategy into a therapy for humans. Promising results were soon reported by several groups, with a landmark clinical trial in 2010 showing significant efficacy in patients with advanced melanoma.
Dr Tasuku Honjo of the Kyoto University, Japan, discovered the PD-1 protein in 1992. With animal studies performed by his team and other groups showing promise, the strategy of PD-1 blockade in cancer treatment soon proceeded to clinical development. In 2012, a key study showed that treatment with an antibody against PD-1 provided long-term remission in patients with several types of metastatic cancer.
The anti–CTLA-4 therapy ipilimumab and anti–PD-1 therapies nivolumab and pembrolilzumab were subsequently approved for use in cancer patients. In clinical trials and clinical practice, these therapies have significantly improved the outcomes of patients with advanced cancers including melanoma, non-small-cell lung cancer, renal cell carcinoma, squamous carcinoma of the head and neck, hepatocellular carcinoma, and urothelial carcinoma. Other immunotherapies, such as durvalumab, atezolizumab and avelumab, have also become available recently.
Current studies are evaluating the combination of anti–CTLA-4 and anti–PD-1 therapies and their combinations with other treatment modalities in various types of cancer.Other cancer therapies have previously been awarded Nobel Prizes, including hormonal treatment for prostate cancer in 1966, chemotherapy in 1988, and bone marrow transplantation in 1990.