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Title: | A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma. | Austin Authors: | Ebert, Lisa M;MacRaild, Sarah E;Zanker, Damien;Davis, Ian D;Cebon, Jonathan S ;Chen, Weisan | Affiliation: | Ludwig Institute for Cancer Research (Melbourne-Austin Branch), Melbourne, Australia | Issue Date: | 26-Oct-2012 | Publication information: | PLoS One 2012; 7(10): e48424 | 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. | Gov't Doc #: | 23110239 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/11600 | DOI: | 10.1371/journal.pone.0048424 | Journal: | PLoS One | URL: | https://pubmed.ncbi.nlm.nih.gov/23110239 | Type: | Journal Article | Subjects: | Cancer Vaccines.therapeutic use Cells, Cultured Epitopes.immunology Flow Cytometry Humans Leukocytes, Mononuclear.metabolism Melanoma.immunology.pathology.therapy T-Lymphocytes, Regulatory.immunology |
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