Cancer Immunotherapy Booster

Cancer research is a rapidly evolving field with new discoveries emerging daily on its biology, prevention, diagnosis, and treatment. In particular, the recent achievement of several key immunotherapy milestones dramatically changed the landscape of cancer treatment. An important advance occurred in 2010, with the US Food and Drug Administration (FDA) approval of the first therapeutic vaccine, Provenge (sipuleucel-T), for advanced prostate cancer, marking a major turning point for the fields of oncoimmunology and precision oncology. The FDA approval of another immune-based drug, Yervoy (ipilimumab) for the treatment of metastatic melanoma, followed in 2011. Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyteassociated protein 4 (CTL4-A), a receptor expressed by activated T cells that negatively regulates their activation. The clinical success of CTLA-4 blockade prompted the development of other drugs targeting immune checkpoint molecules, such as nivolumab and pembrolizumab (programmed cell death protein 1 [PD-1] blockers), which have recently also been approved by the FDA. (For a review on immune checkpoint targeting in cancer see Sharma and Allison, 2015.) Despite the clinical promise of checkpoint blockade immunotherapies, many challenges remain. Cancer is a highly heterogeneous and complex entity that is constantly changing over time, and cancer cells are very good at tricking the immune system, eventually leading to drug resistance and disease progression in some patients. Behind such disconcerting complexity there are, fortunately, opportunities. For instance, sequencing efforts showed that the tumor’s mutational load can influence sensitivity to immune checkpoint blockade (Snyder et al., 2014, Van Allen et al., 2015, Rizvi et al., 2015). As tumors grow, they accumulate mutations, which are a rich source of novel antigens (neoantigens) for the immune system to recognize, favoring effective immune-surveillance and potentially expanding the clinical