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

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 antit...

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Autores principales: Fan, Xiaozhou, Quezada, Sergio A., Sepulveda, Manuel A., Sharma, Padmanee, Allison, James P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978270/
https://www.ncbi.nlm.nih.gov/pubmed/24687957
http://dx.doi.org/10.1084/jem.20130590
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author Fan, Xiaozhou
Quezada, Sergio A.
Sepulveda, Manuel A.
Sharma, Padmanee
Allison, James P.
author_facet Fan, Xiaozhou
Quezada, Sergio A.
Sepulveda, Manuel A.
Sharma, Padmanee
Allison, James P.
author_sort Fan, Xiaozhou
collection PubMed
description 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.
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spelling pubmed-39782702014-10-07 Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy Fan, Xiaozhou Quezada, Sergio A. Sepulveda, Manuel A. Sharma, Padmanee Allison, James P. J Exp Med Article 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. The Rockefeller University Press 2014-04-07 /pmc/articles/PMC3978270/ /pubmed/24687957 http://dx.doi.org/10.1084/jem.20130590 Text en © 2014 Fan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Fan, Xiaozhou
Quezada, Sergio A.
Sepulveda, Manuel A.
Sharma, Padmanee
Allison, James P.
Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title_full Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title_fullStr Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title_full_unstemmed Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title_short Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy
title_sort engagement of the icos pathway markedly enhances efficacy of ctla-4 blockade in cancer immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978270/
https://www.ncbi.nlm.nih.gov/pubmed/24687957
http://dx.doi.org/10.1084/jem.20130590
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