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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:||http://ahro.austin.org.au/austinjspui/handle/1/11600||DOI:||10.1371/journal.pone.0048424||URL:||https://pubmed.ncbi.nlm.nih.gov/23110239||Type:||Journal Article||Subjects:||Cancer Vaccines.therapeutic use
|Appears in Collections:||Journal articles|
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