Harnessing the power of the immune system via blockade of PD-1 and PD-L1: a promising new anticancer strategy. (April 2014)

• Record Type: Journal Article
• Authors: Reiss, Kim A; Forde, Patrick M; Brahmer, Julie R
• Is Part Of: Immunotherapy. Volume 6:Number 4(2014:Apr.)
• Page Start: 459
• Page End: 475
• Publication Date: 2014-04
• Subjects: antibody -- cancer -- checkpoint inhibitor -- immunotherapy -- melanoma -- non-small-cell lung cancer -- PD-1 -- PD-L1/2 -- renal cell carcinoma; Immunotherapy -- Periodicals; 615.37
• DOI: 10.2217/imt.14.9
• Languages: English
• ISSNs: 1750-743X

Abstract

Cancer cells employ several mechanisms to evade the immune system of their host, thus escaping immune recognition and elimination. Of particular interest is a cancer cell's ability to co-opt the immune system's innate ligands and inhibitory receptors (also known as checkpoints), thus creating an immunosuppressive microenvironment that downregulates T-cell activation and cell signaling. The recent development of the checkpoint inhibitors anti-programmed death-1 and anti-programmed death ligand-1 has generated an enormous amount of interest as a potential new anticancer strategy in solid tumors, particularly in non-small-cell lung cancer, renal cell carcinoma and melanoma. Data suggest significant disease response rates using anti-programmed death-1 and anti-programmed death ligand-1 antibodies, even in heavily pretreated patients. Future directions include optimization of drug delivery sequence and combination of immunotherapy with other therapies including cytotoxic chemotherapy, radiation, antiangiogenic agents and small-molecule tyrosine kinase inhibitors.