The Nobel Prize in Physiology or Medicine was awarded to James P. Allison from the University of Texas MD Anderson Cancer Center and Tasuku Honjo from Kyoto University for their discovery of the inhibition of negative immune regulation to aid in cancer therapy.
In the 1990s, James P. Allison and other researchers noticed that the protein CTLA-4 acted to suppress T-cells.
While other researchers focused on the application of this finding on the treatment of autoimmune diseases, Allison decided to explore its application to fight cancer. Using an antibody that he had previously developed, Allison began investigating whether the deactivation of CTLA-4 would lift the brake on T-cells and allow them to attack cancerous cells.
Allison and his team soon discovered that anti-tumor T-cells in mice were released when the antibody was used, thus curing cancer.
In 2010, a clinical trial produced results never before seen in patients with advanced melanoma. Treatment resulted in remaining signs of cancer to disappear.
In 1992, Tasuku Honjo discovered another protein on the surface of T-cells, PD-1. A series of experiments revealed that PD-1 also worked as a T-cell brake, and animal experiments showed promising results in the treatment of cancer. In 2012, a clinical study demonstrated its efficacy in the treatment of different cancers, and treatment resulted in long-term remission. Even metastatic cancer, previously thought to have no cure, was effectively treated.
Such treatment has come to be known as “immune checkpoint therapy,” and trials are still currently underway to treat several types of cancer. The discoveries by both Allison and Honjo have allowed for more rapid development of using a patient’s own immune system to fight cancer more effectively.
The Bloomberg-Kimmel Institute (BKI) for Cancer Immunotherapy at Hopkins is attempting to develop drugs and vaccines to help trigger patients’ immune systems’ natural defenses to recognize and kill cancerous cells.
BKI has labeled the immune system as “the perfect anti-cancer agent” for several reasons: Containing more T-cells and acting more specifically than pharmaceuticals, it uses 16 different molecules to attack cancer cells and remembers how to fight cancer cells in the future.
BKI works with immune checkpoint blockers, which prevent cancer cells from producing certain proteins. This makes it easier for the immune system to recognize those cells as cancer cells and attack them.
According to the BKI, 15 types of cancers respond to this immunotherapy, with some patients seeing their cancer go from stage four to undetectable and others having tumors shrink drastically and stay away for years.
The Sidney Kimmel Comprehensive Cancer Center, the BKI’s parent institution, is accredited with developing anti-PD-1 therapy, a type of checkpoint inhibitor drug.
Therapeutic cancer vaccines are also an active form of treatment at the BKI. They function by calling immune cells to the site of a tumor and causing those immune cells to find and attack additional cancer cells throughout a patient’s body. Therapeutic vaccines differ from preventative vaccines in that they are given to people who already have the target disease instead of to healthy people.
The Sidney Kimmel Comprehensive Cancer Center is currently in clinical trials for a vaccine for pancreatic cancer.
BKI explains that there are a few different approaches to using the vaccine: It can be given before surgery; it can be combined with other immune-modulating drugs; or it can be added to a second kind of vaccine, a weakened version of the bacterium Listeria.
BKI is also currently exploring a form of treatment called personalized cell therapy, which works by increasing the number of disease-fighting immune cells in the body. In order to do this, T-cells are collected from patients treated with antibodies in a laboratory.
The cells are then infused into the patient’s bloodstream, which is a necessary step in facilitating the attack on cancer cells.
BKI reports that Hopkins researchers have recently developed a new type of adoptive T-cell therapy focused on treating high-risk multiple myeloma patients. The procedure collects a specific type of T-cell from the bone marrow, called marrow-infiltrating lymphocytes (MILs), and then uses the MILs in combination with chemotherapy and a stem cell transplant to treat and control the cancer.
The discoveries by the laureates Allison and Honjo and the research being conducted at Hopkins are evidence of the continuous search for advancements of cancer immunotherapy and of the ongoing search for a cure for all cancers.
