Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy

• Published in: Cancer cell Vol. 27; no. 4; pp. 450 - 461
• Main Authors: Topalian, Suzanne L., Drake, Charles G., Pardoll, Drew M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.04.2015
• Subjects: Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; CD28 Antigens - antagonists & inhibitors; CD28 Antigens - immunology; CD28 Antigens - physiology; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; CTLA-4 Antigen - physiology; Humans; Immunotherapy; Models, Immunological; Neoplasms - immunology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - physiology
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccell.2015.03.001

The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study.