Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11600
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
Appears in Collections:Journal articles

Show full item record

Page view(s)

18
checked on Oct 14, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.