Scientifically based combination therapies with immuno-oncology checkpoint inhibitors.

The discovery of immune checkpoints and their role in modulating immune response have revolutionised cancer treatment in recent years. The immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1), have been extensively studied. Currently seven monoclonal antibodies targeting these immune checkpoints are approved for treatment of various cancers. Inhibiting immune checkpoints has shown some success in clinic, however, a proportion of patients do not benefit from this treatment. Several other inhibitory molecules, in addition to CTLA-4 and PD-1, are known to be involved in regulating immune response. In order to further improve patient outcomes, studies have examined targeting these inhibitory molecules through combination therapies. This review discusses the current landscape of combination therapies of checkpoint inhibitors.