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CD59 Blockade Enhances Antigen-Specific CD4⁺ T Cell Responses in Humans: A New Target for Cancer Immunotherapy?¹

Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff, U.K.

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The work was funded by a Wellcome trust project grant awarded to A.M.G. and B.P.M. that supports B.S. (ref. no: 079115). A.M.G. is a Medical Research Council senior research fellow (ref. no. G117/488). M.P.L. is a recipient of Wellcome trust prize studentship (ref. no. 073055). B.P.M. is funded by Wellcome trust program grant (ref. no. 068590).

² Current address: Laboratory of Physiology and Immunology, The Rockefeller University, York Avenue, New York, NY 10021.

³ A.J.G. and A.M.G. contributed equally to this study.

⁴ Address correspondence and reprint requests to Dr. Awen M. Gallimore, Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff, U.K. E-mail address: GallimoreAM{at}cardiff.ac.uk

⁵ Abbreviations used in this paper: C, complement; CRC, colorectal cancer; PPD, purified protein derivative; CEA, carcinoembryogenic Ag; Treg, regulatory T cell.