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PMID: 25440090 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway.

Trends in molecular medicine ·Vol. 21 ·No. 1 ·2015-01-00 ·Pages 24-33

Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X

Abstract

The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.

Keywords
PD-1 PD-L1 PD-L2 human cancer immunotherapy monoclonal antibody
MeSH Terms
Animals Antibodies/therapeutic use B7-H1 Antigen/immunology Humans Immunotherapy Neoplasms/immunology,therapy Programmed Cell Death 1 Receptor/immunology T-Lymphocytes/immunology
Chemicals
Antibodies B7-H1 Antigen CD274 protein, human PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ohaegbulam Kim C
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA.
Assal Amer
Department of Oncology, Montefiore Medical Center, New York, NY 10467, USA.
Lazar-Molnar Eszter
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Yao Yu
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Zang Xingxing
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461, USA; Department of Oncology, Montefiore Medical Center, New York, NY 10467, USA. Electronic address: xing-xing.zang@einstein.yu.edu.
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Article Info
Journal
Trends in molecular medicine
Abbr.
Trends Mol Med
ISSN
1471-499X
DOI
10.1016/j.molmed.2014.10.009
Email
xing-xing.zang@einstein.yu.edu
Published
2015-01-00
Epub
2014-00-30
Pages
24-33
Language
English
Region
England
NLM ID
100966035
PMCID
PMC4282825
Subset
IM
Grants
NCI NIH HHS · F31CA183493 · United States
NCI NIH HHS · F31 CA183493 · United States
NCATS NIH HHS · UL1 TR001073 · United States
NCI NIH HHS · R01 CA175495 · United States
NCI NIH HHS · R01CA175495 · United States
External Links
PubMed source DOI: 10.1016/j.molmed.2014.10.009 PMC Full Text View journal details
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