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J Clin Oncol. 2015 Jun 10;33(17):1974-82. doi: 10.1200/JCO.2014.59.4358. Epub 2015 Jan 20.

Immune Checkpoint Blockade in Cancer Therapy.

Author information

1
All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
2
All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY. wolchokj@mskcc.org.

Abstract

Immunologic checkpoint blockade with antibodies that target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have demonstrated promise in a variety of malignancies. Ipilimumab (CTLA-4) and pembrolizumab (PD-1) are approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways. Treatment with both CTLA-4 and PD-1/PD-L1 blockade is associated with a unique pattern of adverse events called immune-related adverse events, and occasionally, unusual kinetics of tumor response are seen. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade are being investigated to determine whether they enhance the efficacy of either approach alone. Principles learned during the development of CTLA-4 and PD-1/PD-L1 approaches will likely be used as new immunologic checkpoint blocking antibodies begin clinical investigation.

PMID:
25605845
PMCID:
PMC4980573
DOI:
10.1200/JCO.2014.59.4358
[Indexed for MEDLINE]
Free PMC Article

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