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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-36187

Nuber, N; Curioni-Fontecedro, A; Matter, C; Soldini, D; Tiercy, J M; von Boehmer, L; Moch, H; Dummer, R; Knuth, A; van den Broek, M (2010). Fine analysis of spontaneous MAGE-C1/CT7-specific immunity in melanoma patients. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 107(34):15187-15192.

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Abstract

Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7(+)) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4(+) T-cell responses were detected in three patients (11.5%). These CT7-specific CD4(+) T-cell responses were detectable in melanoma patients' PBMCs exclusively from preexisting CD45RA(-) memory CD4(+) T-cell pool. Additional CT7-specific memory CD4(+) T-cell responses were detected in CT7(+) melanoma patients after depletion of CD4(+)CD25high Treg cells showing that Treg cells impact on CT7-specific CD4(+) T cells in melanoma patients. CT7-specific CD4(+) T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
DDC:610 Medicine & health
Language:English
Date:24 August 2010
Deposited On:02 Dec 2010 13:24
Last Modified:13 Dec 2013 11:57
Publisher:National Academy of Sciences
ISSN:0027-8424
Additional Information:Proceedings of the National Academy of Sciences
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1073/pnas.1002155107
PubMed ID:20696919
Citations:Web of Science®. Times Cited: 10
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Scopus®. Citation Count: 11

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