【摘要】 目的比较HPV16型E7抗原CTL表位E711-20(YMLDLQPETT)与其修饰多肽配体APL(YLLDLQPE-VT)诱发特异CTL免疫应答的能力和抗肿瘤免疫治疗的作用。观察E711-20及其APL的小鼠TC-1细胞肿瘤免除率、存活时间与荷瘤小鼠的肿瘤体积变化,了解其预防和治疗效果。方法以E711-20及其修饰多肽配体(APL)免疫C57BL/6小鼠,测定免疫后小鼠脾淋巴细胞的增殖指数;用LDH释放试验检测免疫后小鼠脾淋巴细胞的CTL杀伤活性。结果脾细胞增殖实验中,3组增殖指数如下:IFA+APL组2.42±0.38,IFA+E711-20组1.68±0.32,IFA组1.07±0.22;CTL杀伤效应实验中,3组靶细胞溶破率(%)如下:IFA+APL组54.21±0.12,IFA+E711-20组62.33±0.46,IFA组0.88±0.07;IFA组肿瘤免除率为0,IFA+E711-20组肿瘤免除率为40%,IFA+APL组肿瘤免除率为80%;荷瘤小鼠中,对照组IFA肿瘤体积迅速增大,E711-20和APL组的肿瘤生长速度较慢。APL免疫诱导的小鼠脾淋巴细胞,其CTL杀伤活性和增殖能力强于E711-20;APL对TC-1肿瘤细胞的预防和治疗效果优于E711-20。结论 APL诱导特异性抗肿瘤免疫应答的能力和抗肿瘤效果优于E711-20,可能为针对HPV16E7抗原的肽疫苗分子设计提供理想的CTL表位。更多还原

【Abstract】 Objective To compare the immunogenicity of HPV16 native CTL epitope E711-20( YMLDLQPETT) with its APL ( YLLDLQPEVT) in inducing specific antitumor efficacy and priming specific CTL immune response. C57BL/6 mice were immunized with E711-20 or the APL emulsified in IFA. The rate of tumor-free, survival time,and tumor volume change were observed,to investigate the therapeutic and prophylactic effects to TC-1 tumor. Methods The specific lysis of CTL obtained from mice immunized with E711-20 or APL targeting to TC-1 cells and splenocytes proliferatioin ability induced by E711-20 or the APL in the presence of E711-20 were assessed. Results The proliferation indexes of 3 groups were 2. 42 ± 0. 38 ( IFA + APL) ,1. 68 ± 0. 32( IFA + E711-20) ,1. 07 ± 0. 22( IFA) respectively. The lysis rates ( % ) of target cells were 54. 21 ± 0. 12 ( IFA + APL) ,62. 33 ± 0. 46( IFA + E711-20 ) ,0. 88 ± 0. 07( IFA) . The rates ( % ) of tumor-free were 0( IFA) ,40( IFA + E711-20 ) ,80 ( IFA + APL) . The gross tumor volume developed rapidly,but slowly in the other 2 groups. The specific lysis of CTL targeting to TC-1 cells and splenocytes proliferatioin ability induced by APL were higher than that of E711-20. The therapeutic and prophylactic effect induced by APL were more obvious than E711-20. Conclusion APL has the superior immunogenicity compared with E711-20,and provided ideal CTL epitope for HPV16 peptide-based vaccine design possibly.更多还原