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01.04.2015 | Original Article

Low-dose cyclophosphamide enhances antigen-specific CD4⁺ T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma

verfasst von: Oliver Klein, Ian D. Davis, Grant A. McArthur, Li Chen, Andrew Haydon, Phillip Parente, Nektaria Dimopoulos, Heather Jackson, Kun Xiao, Eugene Maraskovsky, Wendie Hopkins, Rodica Stan, Weisan Chen, Jonathan Cebon

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 4/2015

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Abstract

Clinical outcomes from cancer vaccine trials in patients with advanced melanoma have so far been disappointing. This appears at least partially due to a state of immunosuppression in these patients induced by an expansion of regulatory cell populations including regulatory T cells (Tregs). We have previously demonstrated potent immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine in patients with resected melanoma (study LUD99-08); however, the same vaccine induced only a few vaccine antigen-specific immune responses in patients with advanced disease (study LUD2002-013). Pre-clinical models suggest that the alkylating agent cyclophosphamide can enhance immune responses by depleting Tregs. Therefore, we have enrolled a second cohort of patients with advanced melanoma in the clinical trial LUD2002-013 to investigate whether pre-treatment with cyclophosphamide could improve the immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine. The combination treatment led to a significant increase in vaccine-induced NY-ESO-1-specific CD4⁺ T cell responses compared with the first trial cohort treated with vaccine alone. We could not detect a significant decline in regulatory T cells in peripheral blood of patients 14 days after cyclophosphamide administration, although a decline at an earlier time point cannot be excluded. Our observations support the inclusion of cyclophosphamide in combination trials with vaccines and other immune-modulatory agents.

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Titel: Low-dose cyclophosphamide enhances antigen-specific CD4+ T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma
verfasst von: Oliver Klein
Ian D. Davis
Grant A. McArthur
Li Chen
Andrew Haydon
Phillip Parente
Nektaria Dimopoulos
Heather Jackson
Kun Xiao
Eugene Maraskovsky
Wendie Hopkins
Rodica Stan
Weisan Chen
Jonathan Cebon
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 4/2015
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-015-1656-x

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Low-dose cyclophosphamide enhances antigen-specific CD4⁺ T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma

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