The immune system monitors infection of bacteria, viruses and other microbial pathogens and eliminates them to defend against infectious diseases. This system also surveys from transformed cells to protect against cancer, which is specifically called cancer immunity. Cancer immunotherapies are treatments aimed at enhancing or restoring a patient’s immune system to fight cancer.
Transformed cells express tumor-associated proteins that are rarely found or not present in normal cells. These proteins, which are displayed on the cell surface as antigens, seem to appear foreign to the immune system and trigger the elimination of transformed cells by immune cells. During this immunosurveillance, some tumor cells can develop tolerance to elimination and often stop displaying the tumor-associated antigens, which allows tumor progression to occur. In addition, tumor cells also evade the antitumor response by suppressing the immune system. Because of the immune tolerance and immunosuppressive effects of cancer, numerous attempts to develop effective immunotherapies have failed for several decades. Activating the immune system to achieve a significant therapeutic benefit has long been a goal in cancer immunology.
The tide was turned by the success of proof-of-concept clinical trials of the anti-CTLA4 antibody ipilimumab in 2007. In these trials, patients with metastatic melanoma for whom conventional therapies failed, significantly increased survival. Recent developments in immune checkpoint inhibitor antibodies (anti-PD-1 and anti-PD-L1 antibodies) have revolutionized cancer therapy as they have achieved curative outcomes in cancers that were incurable just several years ago. Science magazine selected the cancer immunotherapy as the “Breakthrough of the Year” for 2013. At present, the overall response rates in patients treated with these immune checkpoint inhibitors remain at 10–30% although numerous attempts have been made to increase the effectiveness. To achieve greater therapeutic benefits, the focus should be on each patient’s pathological and immune status for the most effective, precise cancer immunotherapy.
According to the Pharmaceutical Manufacturers and Research of America (PhRM), as of June 2017, 248 cancer immunotherapy agents are currently under development, including 45 immune checkpoint inhibitors; 21 cell therapy agents, such as CAR-T; 14 oncolytic virus agents; and 96 cancer vaccines. Based on the expanding interest in the field of cancer immunotherapy, these agents are expected to account for ~50% of all cancer therapies by the mid-2020s, and the market is forecast to be worth $100 billion.