Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.

Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.
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CTLA-4 与 HPV16 E7 和 E6 的融合增强了治疗性 HPV DNA 疫苗的效力

DOI:
10.1371/journal.pone.0108892
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Fan M
Fan M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gan L;Jia R;Zhou L;Guo J;Fan M

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预防性抗HPV疫苗对HPV感染有效,但对现有的HPV相关疾病无效,包括宫颈癌和其他恶性疾病。因此,迫切需要开发治疗性疫苗。为了提高治疗性疫苗的抗肿瘤效果,我们将细胞毒性T淋巴细胞抗原4(CTLA-4)与HPV 16 E7、E6融合,构建了融合治疗性DNA疫苗(pCTLA-4-E7 E6)。pCTLA 4-E7 E6在荷TC-1肿瘤的C57 BL/6小鼠体内诱导的特异性抗体和特异性CTL应答均显著高于非融合DNA疫苗pE 7 E6。pCTLA 4-E7 E6在治疗性免疫中的抗肿瘤作用比pE 7 E6强。这些结果表明,融合CTLA-4与E7 E6是一个有用的策略,开发治疗性HPV DNA疫苗。此外,E7的C-末端与E6的N-末端融合损害了E7和E6的功能。
Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4) with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6). pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.
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