The 2018 Nobel Prize in Physiology or Medicine has been awarded jointly to two cancer immunotherapy researchers, James P. Allison, PhD, of The University of Texas MD Anderson Cancer Center, and Dr. Tasuku Honjo of Kyoto University in Japan. Allison and Honjo were honored for their work on uncovering ways to activate the immune system to attack cancer, a breakthrough in developing new cancer treatments. According to Otis W. Brawley, MD, MACP, American Cancer Society Chief Medical Officer, “The discoveries of Honjo and Allison led to the development of several drugs which allow for the routine use of effective immunotherapy.”
Both researchers are being recognized for their work in the 1990s. The two worked separately during their careers to show how certain proteins prevent immune cells called T cells from attacking other cells in the body.
In his laboratory at the University of California, Berkeley, Allison studied the T cell protein CTLA-4. When this protein attaches to another protein (called B7) found on the surface of some cancer cells, it signals the T cell that this cell is functioning properly. As long as a regular or cancer cell is sending the message that it is functioning well, the immune system will not destroy the cell. By blocking the CTLA-4 protein and thereby the message that the cell is working as it should, the immune system can recognize cancer cells and attack them. This discovery eventually led to the drug Yervoy (ipilimumab), which is used to treat melanoma skin cancer and some other cancers.
Honjo at Kyoto University in Japan discovered PD-1, which is another protein found on the surface of some T cells. When this protein attaches to a protein called PD-L1 on cancer cells, it can prevent the T cells from recognizing the cancer cells, so the immune system won’t destroy them. Blocking the PD-L1 protein on cancer cells, or the corresponding PD-1 protein on immune cells, allows the immune system to recognize the cancer cells as foreign and attack them.
These discoveries led to the development of immunotherapy drugs routinely used to treat many other types of cancer. Drugs that target PD-1 include Keytruda (pembrolizumab) and Opdivo (nivolumab), while drugs that target PD-L1 include atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi). These drugs are now used to treat people with many different cancer types, including melanoma skin cancer, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma.
This type of treatment is often referred to as immune checkpoint therapy. According to the Nobel committee, immune checkpoint therapy has revolutionized cancer treatment and has fundamentally changed the outcome for certain groups of patients with advanced cancer.
In 2015, the American Cancer Society awarded Allison the Medal of Honor for his work on immune checkpoint therapy. The Medal of Honor is awarded to those who have made the most valuable contributions and impact in the fight to end cancer through basic research, clinical research, cancer control, or philanthropy. It’s the American Cancer Society’s highest honor.
Brawley says Allison’s work has changed cancer treatment. He said, “Immunotherapy is now considered the fifth pillar of cancer therapy: surgery, radiation, chemotherapy, precision medicine, and immunotherapy. They are often used in combination to effectively treat a number of cancers.”
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