纳米疫苗经不同途径给药后的抗肿瘤免疫学效应比较

Comparison on the antineoplastic immunological effects of nanoemulsion vaccine given throngh different routes

目的比较纳米乳剂包裹的复合抗原NE(MHS)经不同途径免疫小鼠后的抗肿瘤免疫学效应,探索肿瘤疫苗有效的给药途径。方法采用磁力超声法制备纳米疫苗NE(MHS)(融合蛋白MAGE1-HSP70和超抗原SEA按摩尔比100∶1混合),评价其粒径、包裹率及稳定性。以NE(MHS)经口服、皮下、静脉和腹腔注射4种途径免疫C57BL/6小鼠,IFN-γELISPOT和LDH杀伤实验检测小鼠特异性细胞免疫反应情况,肿瘤治疗、攻击实验比较4种不同途径免疫的抗肿瘤效应。结果所制备纳米乳剂为乳白色均质胶体混悬液,粒径为20±5nm,包裹率为87%。B16-MAGE1接种后第28天,口服免疫组小鼠肿瘤体积明显大于其他3组(P<0.05),而小鼠脾淋巴细胞中分泌IFN-γ的特异性T淋巴细胞频数及对B16-MAGE1的杀伤效果、荷瘤小鼠的生存期、小鼠成瘤时间等4组间两两比较均无统计学差异。结论纳米乳剂疫苗NE(MHS)经不同途径给药后对小鼠的抗肿瘤免疫学效应相近,表明其适用于多种途径给药(包括口服),是一种使用方便的肿瘤基因工程纳米疫苗。

Objective To compare the antineoplastie immunological effects of nanoemulsion-encapsulated MAGE1-HSP70 and SEA （the ratio of MAGE1-HSP70 fusion protein to SEA superantigen was 100：1） as NE（MHS） vaccine as given in different routes, and try to look for a novel and effective immune mute. Methods NE （MHS） was prepared using magnetic ultrasound methods, and the size, the encapsulation rate and the stability of the nanoemulsion vaccine were evaluated. C57BL/6 mice were immunized via p. o. , subcut. , i. v. , or i.p. mute. The cellular was detected by ELISPOt assay and LDH release assay. The therapeutic and tumor challenge assay were examined too. Results When the vaccine was given orally, the tumor masses formed 28 days after B16-MAGE1 inoculation in mice were markedly bigger than that formed in the mice of the other groups （P〈0. 05）. On the other hand, the ELISPOt assay, LDH release assay and tumor challenge assay showed no statistical differences on antineoplastic immunological effects in the mice with the vaccine administered via 4 mutes. Conclusion The immune responses seem to be similar in mice inoculated with VE （MHS） via 4 different mutes. Nanoemulsion vaccine can be given via different mutes including p. o. , and it is a convenient vaccine.