Immuno-regulatory antibodies for the treatment of cancer.

INTRODUCTION: After years of limited success, progress of anti-cancer immuno-therapeutics has been considerable over the past decade. Key to this progress has been the application of new biological insights around the importance and nature of immune checkpoints that are able to reverse down-regulation of anti-tumor immunity.

AREAS COVERED: An overview of the preclinical and recent clinical trial data on key immuno-regulatory agents currently in development, including antibody targeting of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death receptor 1 (PD-1) on T-lymphocytes and its principal ligand (PD-L1) on tumor cells as well as immune agonists (e.g., anti-CD40).

EXPERT OPINION: Durable long-term responses in some patients with advanced melanoma, initially with ipilimumab (anti-CTLA-4) and more recently antibodies targeting either PD-1 or PD-L1 in patients with melanoma and renal cancer, non-small-cell lung, bladder and head and neck cancers with less toxicity, have provided real optimism that immunotherapeutic approaches can improve outcomes in a wide range of cancer. The manageable tolerability of PD-1-pathway blockers and their unique mechanism of action are encouraging combination approaches. Current efforts focus on registration trials of single agents plus combinations in many different tumor types and treatment settings and identifying and developing predictive biomarkers of immunological response.