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

   


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:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84897940775&partnerID=40&md5=729858779dff048f2294e801439a20f0
Notes: Export Date: 1 May 2014 -- CODEN: JEMEA -- Source: Scopus
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MSK Authors
  1. Padmanee Sharma
    9 Sharma
  2. James P Allison
    130 Allison
  3. Manuel Alejandro Sepulveda
    6 Sepulveda
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