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
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
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DOI：
10.1016/j.vaccine.2006.06.087
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发表时间：
2007-01-02
期刊：
影响因子：
5.5
通讯作者：
Wu, T-C
中科院分区：
文献类型：
--
作者：
Hung, Chien-Fu;Calizo, Roanne;Wu, T-C
间皮素在大多数卵巢癌细胞中高表达，在正常细胞中低水平表达。因此，间皮素代表了卵巢癌疫苗开发的潜在靶抗原。采用单链三聚体 (SCT) 的 DNA 疫苗已被证明可以绕过抗原加工和呈递，从而显着增强 DNA 疫苗的效力。在当前的研究中，我们使用针对人间皮素的SCT创建了一种DNA疫苗，并表征了随后的抗原特异性CD8（+）T细胞介导的免疫反应和针对HLA-A2转基因小鼠中表达人间皮素的肿瘤的抗肿瘤作用。我们的结果表明，使用与人间皮素表位 aa540-549 (pcDNA3-Hmeso540-beta 2m-A2) 连接的 HLA-A2 SCT 进行 DNA 疫苗接种，在 HLA-A2 转基因小鼠中产生了强烈的人间皮素肽 (aa540-549) 特异性 CD8(+) T 细胞免疫反应。与接种编码与OVA CTL表位相连的SCT的DNA疫苗接种相比，接种pcDNA3-Hmeso540-β 2m-A2可阻止HLA-A2转基因小鼠中表达HLA-A2阳性的人间皮素肿瘤细胞系的生长。因此，使用与人间皮素表位aa540-549连接的HLA-A2的SCT代表了针对人间皮素表达肿瘤（特别是卵巢癌细胞）的DNA疫苗的临床转化的潜在机会。 (c) 2006 Elsevier Ltd. 保留所有权利。
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.