A Dna Vaccine Encoding a Single-chain Trimer of Hla-a2 Linked to Human Mesothelin Peptide Generates Anti-tumor Effects Against Human Mesothelin-expressing Tumors.
From: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. chung2@jhmi.edu
Vaccine
- Publish Date: Jan 2007
- ISSN: 0264-410X
- Volume: 25
- Issue: 1
- Pages: 127-35
- Medium: Print
- Language: English
- Citation (JAMA): Hung Chien-Fu, Calizo Roanne, Tsai Ya-Chea, et al. A Dna Vaccine Encoding a Single-chain Trimer of Hla-a2 Linked to Human Mesothelin Peptide Generates Anti-tumor Effects Against Human Mesothelin-expressing Tumors.. Vaccine Jan 2007;25:127-35
Abstract
Mesothelin is highly expressed in a majority of ovarian cancer cells and is expressed at low levels in normal cells. Therefore, mesothelin represents a potential target antigen for ovarian cancer vaccine development. DNA vaccines employing single-chain trimers (SCT) have been shown to bypass antigen processing and presentation and result in significant enhancement of DNA vaccine potency. In the current study, we created a DNA vaccine employing an SCT targeting human mesothelin and characterized the ensuing antigen-specific CD8+ T cell-mediated immune responses and anti-tumor effects against human mesothelin-expressing tumors in HLA-A2 transgenic mice. Our results showed that vaccination with DNA employing an SCT of HLA-A2 linked to human mesothelin epitope aa540-549 (pcDNA3-Hmeso540-beta2m-A2) generated strong human mesothelin peptide (aa540-549)-specific CD8+ T cell immune responses in HLA-A2 transgenic mice. Vaccination with pcDNA3-Hmeso540-beta2m-A2 prevented the growth of HLA-A2 positive human mesothelin-expressing tumor cell lines in HLA-A2 transgenic mice in contrast to vaccination with DNA encoding SCT linked to OVA CTL epitope. Thus, the employment of SCT of HLA-A2 linked to the human mesothelin epitope aa540-549 represents a potential opportunity for the clinical translation of DNA vaccines against human mesothelin-expressing tumors, particularly ovarian cancer cells.
Mesh Headings (Keywords): Animals, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Line, Tumor, Epitope Mapping, Epitopes, T-Lymphocyte, Female, HLA-A2 Antigen, Humans, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ovarian Neoplasms, Peptides, Vaccination, Vaccines, DNA
Check for Full Text / PubMed Unique Identifier (PMID): 16930783
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