Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+) T cells for
Satoko Matsueda1, Mingjun Wang, Jinsheng Weng
1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
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.
Insights
Researchers identified three prostate-specific G-protein coupled receptor (PSGR)-derived peptides. These peptides activate CD8(+) T cells to target and kill prostate cancer cells, offering potential for new cancer vaccines.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Prostate cancer is a leading cancer in elderly US men.
- Immunotherapy shows promise for metastatic castration-resistant prostate cancer.
- Identifying prostate-specific antigens is key for effective cancer vaccines.
Purpose of the Study:
- To identify novel prostate-specific G-protein coupled receptor (PSGR)-derived peptide epitopes.
- To assess if these epitopes are recognized by CD8(+) T cells in an HLA-A2 dependent manner.
Main Methods:
- An immuno-informatics approach predicted 21 PSGR-derived peptides based on HLA-A2 binding.
- Peptide-specific T cell responses were measured in PBMCs from healthy donors and prostate cancer patients.
- Recognition of PSGR-expressing LNCaP cells by T cells was evaluated.
Main Results:
- Three peptides (PSGR3, PSGR4, PSGR14) induced significant T cell responses in PBMCs from both groups.
- These T cells recognized and killed LNCaP prostate cancer cells.
- The recognition was HLA class I-restricted.
Conclusions:
- Three novel HLA-A2-restricted PSGR-derived peptides were identified.
- These peptides are recognized by CD8(+) T cells that target PSGR(+) tumor cells.
- PSGR-derived peptides may serve as diagnostic markers and targets for prostate cancer vaccines.
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