Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/128421
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Type: | Journal article |
Title: | A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma |
Author: | Ebert, L.M. MacRaild, S.E. Zanker, D. Davis, I.D. Cebon, J. Chen, W. |
Citation: | PLoS One, 2012; 7(10):e48424-1-e48424-10 |
Publisher: | Public Library Science |
Issue Date: | 2012 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Unutmaz, D. |
Statement of Responsibility: | Lisa M. Ebert, Sarah E. MacRaild, Damien Zanker, Ian D. Davis, Jonathan Cebon, Weisan Chen |
Abstract: | Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials. |
Keywords: | Leukocytes, Mononuclear Cells, Cultured Humans Melanoma Cancer Vaccines Epitopes Flow Cytometry T-Lymphocytes, Regulatory |
Rights: | © 2012 Ebert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0048424 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/433608 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0048424 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_128421.pdf | Published version | 1.47 MB | Adobe PDF | View/Open |
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