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J Exp Med. 2014 Apr 7;211(4):715-25. doi: 10.1084/jem.20130590. Epub 2014 Mar 31.

Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy.

Author information

1
Department of Immunology and 2 Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti-CTLA-4 and ICOS engagement.

PMID:
24687957
PMCID:
PMC3978270
DOI:
10.1084/jem.20130590
[Indexed for MEDLINE]
Free PMC Article

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