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Title: Low-dose cyclophosphamide enhances antigen-specific CD4(+) T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma.
Authors: Klein, Oliver;Davis, Ian D;McArthur, Grant A;Chen, Li;Haydon, Andrew;Parente, Phillip;Dimopoulos, Nektaria;Jackson, Heather M;Xiao, Kun;Maraskovsky, Eugene;Hopkins, Wendie;Stan, Rodica;Chen, Weisan;Cebon, Jonathan S
Affiliation: Ludwig Institute for Cancer Research (Melbourne-Austin Branch), 147-163 Studley Road, Heidelberg, VIC, 3084, Australia,
Issue Date: 7-Feb-2015
Citation: Cancer Immunology, Immunotherapy : Cii 2015; 64(4): 507-18
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.
Internal ID Number: 25662405
DOI: 10.1007/s00262-015-1656-x
Type: Journal Article
Appears in Collections:Journal articles

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