Authors: | Fan, X.; Quezada, S. A.; Sepulveda, M. A.; Sharma, P.; Allison, J. P. |
Article Title: | Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy |
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. © 2014 Fan et al. |
Keywords: | controlled study; treatment response; unclassified drug; human cell; drug efficacy; drug potentiation; nonhuman; cancer patient; cancer staging; cd8 antigen; transcription factor foxp3; cd8+ t lymphocyte; animal cell; mouse; cancer immunotherapy; melanoma; animal experiment; animal model; antineoplastic activity; monoclonal antibody; prostate cancer; gamma interferon; cd4+ t lymphocyte; tumor immunity; cd4 antigen; tumor cell vaccine; cytotoxic t lymphocyte antigen 4; inducible t cell costimulator ligand; inducible t cell costimulator; monoclonal antibody 9h10; human; priority journal; article |
Journal Title: | Journal of Experimental Medicine |
Volume: | 211 |
Issue: | 4 |
ISSN: | 0022-1007 |
Publisher: | Rockefeller University Press |
Date Published: | 2014-04-07 |
Start Page: | 715 |
End Page: | 725 |
Language: | English |
DOI: | 10.1084/jem.20130590 |
PROVIDER: | scopus |
PMCID: | PMC3978270 |
PUBMED: | 24687957 |
DOI/URL: | |
Notes: | Export Date: 1 May 2014 -- CODEN: JEMEA -- Source: Scopus |