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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein
A Kiessling1, S Stevanovic, S Füssel
1Institute of Immunology, Medical Faculty, Technical University of Dresden, Fetscherstr. 74, Dresden 01307, Germany.
Abstract:
The development of T-cell-based immunotherapies of cancer largely depends on the availability of tumour-associated antigens capable of eliciting tumour-directed cytotoxic T-cell responses. In prostate cancer, the number of antigens defined as suitable targets of cytotoxic T lymphocytes (CTLs) is still limited. Recently, prostein was identified as a transmembrane protein that is highly restricted to prostate tissues. In our study, prostein transcripts were found to be abundant in both malignant and nonmalignant prostate tissue samples. To identify immunogenic CD8+ T-cell epitopes, human leucocyte antigen-A(*)0201-binding peptides were selected from the amino-acid sequence of prostein and were used for the in vitro stimulation of CD8+ T lymphocytes. Specific CTLs were raised against the prostein-derived peptide CLAAGITYV that were capable of lysing prostate cancer cells, indicating that this peptide is naturally generated by tumour cells. Our data suggest that prostein is a suitable candidate to be included in a T-cell-based immunotherapy of prostate cancer.
Insights
Prostein, a prostate-specific protein, yields a peptide that effectively targets prostate cancer cells. This finding supports prostein as a potential target for T-cell immunotherapies against prostate cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- T-cell-based cancer immunotherapies require well-defined tumor-associated antigens.
- Identifying effective targets for prostate cancer immunotherapy remains a challenge.
- Prostein, a prostate-restricted transmembrane protein, has emerged as a potential candidate.
Purpose of the Study:
- To investigate prostein as a source of immunogenic epitopes for prostate cancer immunotherapy.
- To identify specific peptides derived from prostein that can elicit cytotoxic T-cell responses.
Main Methods:
- Prostein transcript abundance was analyzed in prostate tissues.
- Human leukocyte antigen-A(*)0201-binding peptides were selected from the prostein sequence.
- CD8+ T lymphocytes were stimulated in vitro with prostein-derived peptides.
- Cytotoxic T lymphocyte (CTL) activity against prostate cancer cells was assessed.
Main Results:
- Prostein transcripts were abundant in both malignant and nonmalignant prostate tissues.
- A specific prostein-derived peptide (CLAAGITYV) induced CTLs.
- These CTLs demonstrated the ability to lyse prostate cancer cells.
- The identified peptide is naturally processed and presented by tumor cells.
Conclusions:
- Prostein is a promising tumor-associated antigen for prostate cancer.
- The peptide CLAAGITYV is a potential target for T-cell-based immunotherapy.
- Prostein warrants further investigation for its inclusion in prostate cancer treatment strategies.
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