Scientifically based combination therapies with immuno‐oncology checkpoint inhibitors

Abstract

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, programmed cell death protein 1 and its ligand, programmed cell death‐ligand 1, have been extensively studied. Currently 7 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 lymphocyte‐associated protein 4 and programmed cell death protein 1, are known to be involved in regulating immune response. 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.

Taking the brake off the immune system: Hypotheses, trials, tribulations, and the evolving discipline of clinical immunopharmacology

“…The discovery and development of immune checkpoint inhibitors, cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) inhibitors, programmed cell death protein 1 (PD‐1) inhibitors , and programmed cell death‐ligand 1 (PD‐L1) inhibitors are comprehensively reviewed by Chew et al 7 These authors noted that some of these agents have shown a wide range of benefits but also considerable toxicities in the clinic and emphasize that many patients with solid tumours do not benefit. Although immunotherapy agent dosing is still being optimized, Chew et al note that as well as anti‐CTLA‐4 and anti‐PD‐1, there are several other inhibitory membrane proteins involved in regulating the immune response which could be targeted.…”