肿瘤基因工程纳米疫苗NL(MH)抗肿瘤复发的实验研究

Study on protective effects against tumor relapse induced by nanoliposome - encapsulated tumor specific antigen MAGE3/HSP70[NL(MH)]

目的:在小鼠体内观察纳米疫苗NL(MH)抗肿瘤复发作用。方法:以PBS、空白脂质体、MH、MH/NL、NL(MH)免疫C57BL/6小鼠3次后,IFN-γELISPOT和LDH杀伤实验检测纳米疫苗激活小鼠特异性细胞免疫反应的情况;以肿瘤攻击实验和肿瘤切除后复发实验来评价纳米疫苗预防肿瘤复发作用。结果:与对照组相比,NL(MH)组小鼠脾淋巴细胞中分泌IFN-γ的T细胞数量明显增多(P<0.05),CTL对B16-MAGE3细胞具有显著的特异性杀伤作用;在肿瘤攻击实验中,NL(MH)组B16-MAGE3肿瘤成瘤时间长、成瘤率低;肿瘤切除后,NL(MH)组B16-MAGE3肿瘤复发时间延迟,复发率明显降低。结论:NL(MH)能够刺激机体产生强烈的MAGE3特异性的细胞免疫反应,对表达MAGE3的肿瘤细胞具有显著的杀伤作用,能有效预防B16-MAGE3切除后复发。

Objective ：To evaluate the protective effects against tumor relapse induced by nanoliposome vaccine. Methods： The C57BL/6 mice were immunized with PBS, NL（nanoliposome - unencapsulated tumor specific antigen MAGE3/HSP70） , MH/NL（ MAGE3/HSP70 and NL） , MH, NL（MH）. The spleen lymphocytes secreting IFN - γ, the cyto -toxicity of CTL to B16 - MAGE3 were measured by ELISPOT, LDH release assay to evaluate the cellular- activating effects. The protective and therapeutic effects against tumor metastasis were detected using artifical metastasis experiment mold and spontaneitie metastasis experiment mold; The protective effects against tumor relapse were detected using tumor cells challenge experiments and tumor cut experiment. Results： After the C57BL/6 mice were immunized with NL（MH） , there was the most frequency of MAGE3 specific CTL, highest cytotoxicity of CTL to B16- MAGE3 cells. The metastasis tumor numbers of C57BL/6 mice were immunized with NL（MH） were minimum. Conclusion： NL（MH） can elicit MAGE3 -specific cellular-immune response and antitumor effects against the MAGE3 - expressing tumor. NL（MH） could significantly protect mice effectively from tumor relapse and metastasis.