表达HPV16 E6和E7蛋白的非复制型重组痘苗病毒诱发的抗肿瘤免疫反应

Non-replicating recombinant vaccinia virus expressing HPV16 E6 and E7 proteins elicits anti-tumor immunity in mice

目的 观察表达人乳头瘤病毒 (HPV) 16E6和E7蛋白的非复制型重组痘苗病毒的抗肿瘤免疫效果。方法 以重组痘苗病毒NTVJmE6E7免疫C5 7BL/ 6小鼠 ,检测特异性的细胞毒性T淋巴细胞 (CTL)活性 ;经免疫后的小鼠以TC 1肿瘤细胞攻击 ,观察免疫保护效果 ;荷瘤小鼠切除肿瘤后接种重组痘苗病毒 ,观察肿瘤复发情况。结果 以重组痘苗病毒NTVJmE6E7免疫小鼠 ,可诱导产生针对TC 1细胞的特异性的CTL反应 ;加强免疫后的小鼠能耐受 1× 10 4TC 1细胞的攻击 ;以重组痘苗病毒NTVJmE6E7免疫肿瘤术后小鼠 ,能有效地预防肿瘤复发。结论 非复制型重组痘苗病毒NTVJmE6E7可作为HPV16的相关肿瘤及其癌前病变免疫治疗的候选疫苗。

Objective To investigate the anti tumor immunity of the non replicating recombinant vaccinia virus expressing HPV16 E6 and E7 proteins. Methods C57BL/6 mice were immunized by non replicating recombinant vaccinia virus (NTVJmE6E7), and then specific CTLs were determined. Immune protection effects were evaluated by challenges of different doses of TC 1 tumor cells. Immunotherapeutic effects in form of recurrence were evaluated on the tumor removed mice. Results Mice immunized by NTVJmE6E7 could generate TC 1 cell specific cytotoxic T lymphocyte(CTL). Mice boosted with NTVJmE6E7 could tolerate the challenge of 1×10 4 TC 1 cells. NTVJmE6E7 could effectively prevent the tumor recurrence in the tumor removed mice. Conclusion NTVJmE6E7 can be taken as a candidate of therapeutic vaccine for HPV associated tumors and their precursor lesions. [