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与E7肿瘤抗原相关的结缔组织生长因子通过抗凋亡机制产生强大的抗肿瘤免疫反应。

Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

作者信息

Cheng W-F, Chang M-C, Sun W-Z, Lee C-N, Lin H-W, Su Y-N, Hsieh C-Y, Chen C-A

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Gene Ther. 2008 Jul;15(13):1007-16. doi: 10.1038/gt.2008.25. Epub 2008 Mar 20.

Abstract

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

摘要

一种使用DNA疫苗生成抗原特异性癌症疫苗和免疫疗法的新方法已经出现。然而,抗原呈递细胞(APC)寿命有限,这阻碍了它们长期启动抗原特异性T细胞的能力。结缔组织生长因子(CTGF)在细胞存活中发挥作用。本研究探索了将编码CTGF的DNA与模型肿瘤抗原人乳头瘤病毒16型E7进行皮内给药。用CTGF/E7 DNA疫苗接种的小鼠中,E7特异性CD4(+)和CD8(+) T细胞前体显著增加。与用野生型E7 DNA疫苗接种的小鼠相比,它们对表达E7的肿瘤也表现出令人印象深刻的抗肿瘤作用。递送编码CTGF和E7的DNA或单独的CTGF可延长转导的树突状细胞(DC)在体内的存活时间。此外,与E7转导的DC相比,CTGF/E7转导的DC可增强更多数量的E7特异性CD8(+) T细胞。通过延长APC的存活时间,与肿瘤抗原相连的编码CTGF的DNA疫苗是一种增强DNA疫苗效力的创新方法,有望用于癌症预防和免疫治疗。

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