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

被引：52

作者：

Hung, Chien-Fu

Calizo, Roanne

Tsai, Ya-Chea

He, Liangmei

Wu, T-C

机构：

[1] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[2] Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA

[3] Johns Hopkins Med Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[4] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA

来源：

VACCINE | 2007年 / 25卷 / 01期

关键词：

DNA vaccine; immunotherapy; human mesothelin; single-chain trimer;

D O I：

10.1016/j.vaccine.2006.06.087

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta 2m-A2) generated strong human mesothelin peptide (aa540-549)-specific CD8(+) T cell immune responses in HLA-A2 transgenic mice. Vaccination with pcDNA3-Hmeso540-beta 2m-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. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：127 / 135

页数：9

共 17 条

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