Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations
Top Cited Papers
Open Access
- 23 January 2018
- journal article
- review article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 6 (1), 8
- https://doi.org/10.1186/s40425-018-0316-z
Abstract
Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.Keywords
This publication has 93 references indexed in Scilit:
- Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in MelanomaThe New England Journal of Medicine, 2013
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerThe New England Journal of Medicine, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Continuous systemic corticosteroids do not affect the ongoing regression of metastatic melanoma for more than two years following ipilimumab therapyMedical Oncology, 2010
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- THE B7 FAMILY REVISITEDAnnual Review of Immunology, 2005
- Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockadeProceedings of the National Academy of Sciences of the United States of America, 2002
- Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasionNature Medicine, 2002
- Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte ActivationThe Journal of Experimental Medicine, 2000
- Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytesInternational Immunology, 1996