Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models.

Genetic Vaccines and Therapy Pub Date : 2009-06-21 DOI:10.1186/1479-0556-7-10

Ke Xie, Rui-Zhen Bai, Yang Wu, Quan Liu, Kang Liu, Yu-Quan Wei

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引用次数: 1

Abstract

Background: Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.

Methods: The protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity.

Results: The DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1.

Conclusion: Our study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.

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基于人vegfr -2的DNA疫苗在小鼠模型中的抗肿瘤作用

背景:血管内皮生长因子(VEGF)及其受体VEGFR-2 (Flk-1/KDR)在肿瘤血管生成中起关键作用。阻断VEGF-VEGFR-2通路可能抑制肿瘤生长。在这里，我们使用人VEGFR-2作为模型抗原，探索基于该受体异种同源物的质粒DNA疫苗免疫治疗的可行性。方法:采用小鼠模型研究DNA疫苗的保护作用和抗肿瘤免疫治疗作用。通过免疫组化染色和海藻酸包埋肿瘤细胞实验检测抗血管生成作用。DNA疫苗的作用机制主要通过检测自身抗体和CTL活性来探索。结果:DNA疫苗通过刺激针对mFlk-1的抗原特异性应答，在小鼠模型中通过抗血管生成机制引发了强大的保护性和治疗性抗肿瘤免疫。结论:我们的研究表明，基于异种同源质粒DNA的DNA疫苗可诱导针对VEGFR-2的自身免疫，从而抑制肿瘤生长。这类疫苗可能与癌症免疫治疗具有临床相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Genetic Vaccines and Therapy

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