Title |
Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations
|
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Published in |
Journal for Immunotherapy of Cancer, January 2018
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DOI | 10.1186/s40425-018-0316-z |
Pubmed ID | |
Authors |
Jun Gong, Alexander Chehrazi-Raffle, Srikanth Reddi, Ravi Salgia |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 40 | 34% |
Spain | 7 | 6% |
France | 5 | 4% |
Australia | 4 | 3% |
Mexico | 4 | 3% |
United Kingdom | 4 | 3% |
Brazil | 3 | 3% |
Saudi Arabia | 2 | 2% |
Guinea | 1 | <1% |
Other | 3 | 3% |
Unknown | 43 | 37% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 64 | 55% |
Scientists | 33 | 28% |
Practitioners (doctors, other healthcare professionals) | 15 | 13% |
Science communicators (journalists, bloggers, editors) | 4 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 971 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 142 | 15% |
Student > Ph. D. Student | 140 | 14% |
Student > Bachelor | 103 | 11% |
Student > Master | 94 | 10% |
Other | 54 | 6% |
Other | 130 | 13% |
Unknown | 308 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 178 | 18% |
Biochemistry, Genetics and Molecular Biology | 177 | 18% |
Immunology and Microbiology | 65 | 7% |
Agricultural and Biological Sciences | 64 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 49 | 5% |
Other | 99 | 10% |
Unknown | 339 | 35% |