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J Leukoc Biol. 2013 Jul;94(1):41-53. doi: 10.1189/jlb.1212631. Epub 2013 May 10.

At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy.

Author information

1
Melanoma and Sarcoma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA.

Abstract

It is increasingly appreciated that cancers are recognized by the immune system, and under some circumstances, the immune system may control or even eliminate tumors. The modulation of signaling via coinhibitory or costimulatory receptors expressed on T cells has proven to be a potent way to amplify antitumor immune responses. This approach has been exploited successfully for the generation of a new class of anticancer therapies, "checkpoint-blocking" antibodies, exemplified by the recently FDA-approved agent, ipilimumab, an antibody that blocks the coinhibitory receptor CTLA-4. Capitalizing on the success of ipilimumab, agents that target a second coinhibitory receptor, PD-1, or its ligand, PD-L1, are in clinical development. Lessons learned from treating patients with CTLA-4 and PD-1 pathway-blocking antibodies will be reviewed, with a focus on concepts likely to inform the clinical development and application of agents in earlier stages of development. See related review At the bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.

KEYWORDS:

endpoints; overall survival; tumor

PMID:
23667165
PMCID:
PMC4051187
DOI:
10.1189/jlb.1212631
[Indexed for MEDLINE]
Free PMC Article

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