HPV16型E7复制型DNA疫苗诱发的抗肿瘤免疫反应

Human Papillomavirus Type 16 E7 Suicidal DNA Vaccine Elicits Immunity Against Tumor Cells in Mice

为了研制有效的疫苗 ,用于HPV16型重度感染和与其感染相关的宫颈癌晚期病人手术后的免疫治疗 ,用复制型DAN疫苗载体 pSCA1,在其CMVIE启动子之下插入修饰的HPV16型E7基因mE7- 3( 2 4G、2 6G、6 7R) ,构建成 pSCA1mE7- 3复制型DNA疫苗。以重组质粒免疫C5 7BL/ 6小鼠 ,检测诱发的特异性CTL活性 ;将免疫后的小鼠用TC - 1肿瘤细胞攻击 ,观察免疫保护效果。实验结果显示 :pSCA1mE7- 3复制型DNA疫苗能诱导小鼠产生针对TC - 1肿瘤细胞的特异性CTL反应 ;复制型DNA疫苗免疫后的小鼠能耐受 1× 10 4 TC - 1细胞的攻击 ,成瘤时间推迟 ,并且成瘤率明显下降 ,部分小鼠得到保护能免受肿瘤攻击。因此pSCA1mE7- 3复制型DNA疫苗可作为HPV16相关肿瘤的癌前病变及中晚期病人术后免疫治疗的候选疫苗。

To develop an effective HPV16 therapeutic vaccine for HPV16-associated tumors and their precursor lesions,the suicidal DNA vaccine pSCA1mE7-3 was constructed,which contained the HPV16mE7-3(25G,26G,67R)ORF under the control of the CMV IE promoter.The immuno-protective activity of the vaccine was determined by CTL induction and tumor growth inhibition in vaccine-immunized syngenic mice.Our results indicated that this suicidal DNA vaccine generated E7-specific cytotoxic T-lymphocyte response in vaccinated mice.In vivo tumor protection experiments against the growth of TC-1 tumor,the data showed vaccination with pSCA1mE7-3 suicidal DNA could induce protective immunity in mice challenged with TC-1 tumor cells,the growth of TC-1 tumor was inhibited,and the time of tumor growing was prolonged.It suggested that pSCA1mE7-3 suicidal DNA vaccine can be taken as a candidate of HPV16 therapeutic vaccine.