Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing 100005, P.R. China.
Oncol Rep. 2013 Dec;30(6):3020-6. doi: 10.3892/or.2013.2742. Epub 2013 Sep 20.
Millions of women are currently infected with high-risk human papillomavirus (HPV), which is considered to be a major risk factor for cervical cancer. Thus, it is urgent to develop therapeutic vaccines to eliminate the established infections or HPV-related diseases. In the present study, using the mycobacterium tuberculosis heat shock protein 70 (MtHSP70) gene linked to the modified HPV 16 E7 (mE7) gene, we generated two potential therapeutic HPV DNA vaccines, mE7/MtHSP70 and SigmE7/MtHSP70, the latter was linked to the signal peptide gene sequence of human CD33 at the upstream of the fusion gene. We found that vaccination with the mE7/MtHSP70 DNA vaccine induced a stronger E7-specific CD8+ T cell response and resulted in a more significant therapeutic effect against E7-expressing tumor cells in mice. Our results demonstrated that HSP70 can play a more important role in mE7 and MtHSP70 fusion DNA vaccine without the help of a signal peptide. This may facilitate the use of HSP70 and serve as a significant reference for future study.
目前,数以百万计的女性感染了高危型人乳头瘤病毒(HPV),HPV 被认为是宫颈癌的主要危险因素。因此,迫切需要开发治疗性疫苗来消除已建立的感染或 HPV 相关疾病。在本研究中,我们使用结核分枝杆菌热休克蛋白 70(MtHSP70)基因与改良的 HPV 16 E7(mE7)基因相连,生成了两种潜在的治疗性 HPV DNA 疫苗,mE7/MtHSP70 和 SigmE7/MtHSP70,后者在融合基因的上游与人类 CD33 的信号肽基因序列相连。我们发现,接种 mE7/MtHSP70 DNA 疫苗可诱导更强的 E7 特异性 CD8+ T 细胞反应,并在小鼠中对表达 E7 的肿瘤细胞产生更显著的治疗效果。我们的研究结果表明,HSP70 可以在没有信号肽帮助的情况下,在 mE7 和 MtHSP70 融合 DNA 疫苗中发挥更重要的作用。这可能有助于 HSP70 的应用,并为未来的研究提供重要参考。