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Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein trp-p8
Andrea Kiessling1, Susanne Füssel, Marc Schmitz
1Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany.
Background:
New concepts for the immunotherapy of prostate carcinoma (PCa) largely depend on the identification of suitable target antigens that are present in a high percentage of prostate tumors. Their expression in normal tissues should be restricted to the prostate and they should be immunogenic in vivo. The number of antigens displaying these properties is still limited. Here, we identify for the first time an immunogenic peptide derived from the prostate-specific protein transient receptor potential-p8 (trp-p8) that is recognized by cytotoxic T lymphocytes (CTLs) from PCa patients.
Methods:
To determine the abundance of trp-p8 in prostate tumors, the expression level of trp-p8 mRNA was quantitatively analyzed in a panel of prostate cancer tissues. Trp-p8-derived human leukocyte antigen (HLA)-A*0201-restricted peptides were selected and tested for the in vitro activation of CTLs when loaded on autologous dendritic cells (DCs).
Results:
Trp-p8 mRNA was found to be expressed in all prostate tumors and in the corresponding normal prostate tissue. Of five selected trp-p8-derived peptides, only peptide GLMKYIGEV was shown to activate specific CTLs, which effectively lysed PCa cells confirming the endogenous generation and presentation of this peptide by tumor cells.
Conclusions:
Our results suggest this antigen as a suitable target for the T-cell-based immunotherapy of PCa.
Insights
Researchers identified a novel immunogenic peptide from the prostate-specific protein trp-p8. This peptide is recognized by cytotoxic T lymphocytes (CTLs) in prostate cancer patients, suggesting its potential for immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Effective prostate cancer (PCa) immunotherapy requires identifying target antigens with high tumor expression and restricted normal tissue presence.
- Currently, the number of suitable antigens for PCa immunotherapy is limited.
Purpose of the Study:
- To identify and characterize a novel immunogenic peptide from the prostate-specific protein transient receptor potential-p8 (trp-p8) for PCa immunotherapy.
- To assess the recognition of trp-p8-derived peptides by cytotoxic T lymphocytes (CTLs) from PCa patients.
Main Methods:
- Quantitative analysis of trp-p8 mRNA expression in prostate cancer tissues.
- Selection and in vitro testing of trp-p8-derived peptides for CTL activation using autologous dendritic cells (DCs).
Main Results:
- Trp-p8 mRNA is expressed in all analyzed prostate tumors and corresponding normal prostate tissues.
- A specific trp-p8-derived peptide (GLMKYIGEV) activated CTLs that effectively lysed PCa cells.
- Tumor cells confirmed endogenous generation and presentation of the identified peptide.
Conclusions:
- The identified trp-p8-derived peptide is a promising target for T-cell-based immunotherapy of prostate cancer.
- This finding expands the repertoire of potential antigens for PCa treatment strategies.
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