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CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new target for cancer immunotherapy?

Baalasubramanian, Sivasankar, Longhi, M. Paula, Gallagher, Kathleen M. E., Betts, Gareth J., Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676, Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 2009. CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new target for cancer immunotherapy? The Journal of Immunology 182 (9) , pp. 5203-5207. 10.4049/jimmunol.0804243

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Abstract

CD59, a broadly expressed GPI-anchored molecule, regulates formation of the membrane attack complex of the complement cascade. We previously demonstrated that mouse CD59 also down-modulates CD4+ T cell activity in vivo. In this study, we explored the role of CD59 on human CD4+ T cells. Our data demonstrate that CD59 is up-regulated on activated CD4+ T cells and serves to down-modulate their activity in response to polyclonal and Ag- specific stimulation. The therapeutic potential of this finding was explored using T cells isolated from colorectal cancer patients. The findings were striking and indicated that blockade of CD59 significantly enhanced the CD4+ T cell response to two different tumor Ags. These data highlight the potential for manipulating CD59 expression on T cells for boosting weak immune responses, such as those found in individuals with cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 07 Dec 2022 07:23
URI: https://orca.cardiff.ac.uk/id/eprint/29596

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