Targeting T Cell Co-receptors for Cancer Therapy

Checkpoint-blocking antibodies can generate potent anti-tumor responses by encouraging the immune system to seek and destroy cancer cells. At this time, the United States Food and Drug Administration has approved three checkpoint-blocking antibodies in three disease indications, and additional approvals are expected to broaden the clinical scope of immunotherapy. Herein, we review the clinical development of CTLA-4-, PD-1-, and PD-L1-blocking antibodies across tumor types and briefly discuss areas of active investigation of potential biomarkers. Targeting molecules that regulate T cell activity is an approach that has been translated into potent cancer therapies. Callahan, Postow, and Wolchok review the clinical development of PD-1-, PD-L1-, and CTLA-4-blocking antibodies. They review the clinical activity of agents in development and toxicities associated with this novel approach and summarize recent developments in the search for biomarkers to guide the clinical use of these drugs.