BACKGROUND: Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer.
Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8+ T cells in an HLA-A2 dependent manner.
METHODOLOGY/PRINCIPAL FINDINGS: Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2+ healthy donors or HLA-A2+ prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner.
CONCLUSIONS/SIGNIFICANCE: We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8+ T cells, which, in turn, recognize HLA-A2+ and PSGR+ tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.
Written by:
Matsueda S, Wang M, Weng J, Li Y, Yin B, Zou J, Li Q, Zhao W, Peng W, Legras X, Loo C, Wang RF, Wang HY. Are you the author?
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Reference: PLoS One. 2012;7(9):e45756.
doi: 10.1371/journal.pone.0045756
PubMed Abstract
PMID: 23029225
UroToday.com Investigative Urology Section
