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PMID: 25858804 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Immune checkpoint blockade: a common denominator approach to cancer therapy.

Cancer cell ·Vol. 27 ·No. 4 ·2015-04-13 ·Pages 450-61

Topalian SL, Drake CG, Pardoll DM

Abstract

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.

MeSH Terms
Antibodies, Monoclonal/pharmacology,therapeutic use Antineoplastic Agents/pharmacology,therapeutic use CD28 Antigens/antagonists & inhibitors,immunology,physiology CTLA-4 Antigen/antagonists & inhibitors,immunology,physiology Humans Immunotherapy Models, Immunological Neoplasms/immunology Programmed Cell Death 1 Receptor/antagonists & inhibitors,immunology,physiology
Chemicals
Antibodies, Monoclonal Antineoplastic Agents CD28 Antigens CTLA-4 Antigen Programmed Cell Death 1 Receptor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Topalian Suzanne L
Department of Surgery, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: stopali1@jhmi.edu.
Drake Charles G
The Brady Urological Institute, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Pardoll Drew M
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccell.2015.03.001
Email
stopali1@jhmi.edu
Published
2015-04-13
Epub
2015-00-06
Pages
450-61
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC4400238
Subset
IM
Grants
NCI NIH HHS · R01 CA142779 · United States
NCI NIH HHS · R01 CA154555 · United States
NCI NIH HHS · R01CA142779 · United States
External Links
PubMed source DOI: 10.1016/j.ccell.2015.03.001 PMC Full Text View journal details
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