On October 1 this year, James P. Allison and Tasuku Honjo were awarded to share the Nobel Prize in Physiology or Medicine for their remarkable efforts in cancer checkpoint blockade therapy by inhibiting negative immune regulation. Allison with his colleagues identified cytotoxic T-lymphocyte antigen 4 (CTLA-4) which was a receptor on T cells that prevent them from attacking tumors, while Honjo discovered another key brake on T cells called program death 1 (PD-1). Blockade of both pathways using antibodies or small molecules were shown to significantly enhance anti-tumor immune responses. This award acknowledged immunotherapy as a landmark for fighting cancer or viral infection and inspired researchers to explore more beneficial strategies in clinical trials.
What is immunotherapy? It’s a therapy to use our body’s own immune system to help fight cancer, and this actually has been a long studied area for decades. Besides a number of well-known approaches for cancer treatment, for example chemotherapy, surgery, and radiation, immunotherapy does bring us new light for beating cancer. Under normal physiological conditions, immune cells stay in dynamic balanced status where they could not only eliminate invading pathogens (foreign cells), but also coexist with self-antigens (normal cells). However, tumor cells were found to escape from immune attack in multiple ways. In reference to different mechanisms for cancer cells to survive, there are various types of immunotherapy, including CAR T therapy, cancer vaccines, and checkpoint inhibitors. CAR T therapy is to engineer your T cells (one of the most important immune cells) in the lab to help them identify cancer cells and put them back to your body.
Figure 1. Schematic explanation of how immunotherapy works. Tumors cells could escape from immune attack (for example, switching T cell off) while immunotherapy would help our immune cells recognize them and fight them again.
Cancer vaccines, as it called, create vaccines based on cancer cells’ antigens and immunize your body to attack against cancer cells. Checkpoint inhibitors are used to enhance immune responses by activating or deactivating regulators of immune homeostasis. CTLA-4 and PD-1, as mentioned before, are two most famous and well-studied checkpoint proteins. The CTLA-4 antibodies was the first class of immunotherapeutics approved by U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011. Later on, inhibitors of other immune-checkpoint proteins, such as lambrolizumab which specifically targets PD-1, were applied to patients with advanced or unresectable melanoma who fail to respond to other therapies, and followed with more other checkpoint protein antibodies. Some antibodies were also evaluated in viral infection cases such as HIV infection. Studies in mice and rhesus macaques had resulted with tolerated responses and transient viral control.
With emerging bench data and clinical data indicating the effectiveness and feasibility of immunotherapy, it has become a mainstream field in cancer treatment and hopefully also in viral infection treatment in the near future. Although many challenges remained unsolved and combination approaches under development, we’re confident to witness this new area comes to its age.