Immune checkpoint-targeted cancer immunotherapies

Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system. Their blockade would overcome immune tolerance in the tumor microenvironment and amplify antitumor immunity. What's more, immune checkpoint blockade may turn out even more profitable, as some of immune checkpoints and their ligands are expressed on tumor surface and on tumor infiltrating lymphocytes, contributing to the immunosuppressive cancer microenvironment. Phase III clinical trials have confirmed efficacy of an anti-CTLA-4 antibody ipilimumab, thereby leading to its acceptance for the treatment of advanced melanoma. Thanks to promising results of the phase I clinical trials, a breakthrough therapy designation and an early approval for the treatment have been granted to anti-PD-1 antibodies - nivolumab (for the treatment of advanced melanoma and advanced non-small cell lung cancer) and pembrolizumab (for the treatment of advanced melanoma) and, in the treatment of advanced bladder cancer, an anti-PD-L1 antibody - MPDL3280A as well. Other immune checkpoints, such as LAG-3, TIM-3, BTLA, B7-H3 and B7-H4, are also under early evaluation.