小细胞肺癌抗独特型疫苗功能的试验研究  

Experimental induction of immunity by anti-idiotypic vaccines against small-cell-lung cancer

作　　者：李勇[1] 胡晶莹[2] 张毅[2] 朱明洁[2] 赵新泰[2] 

机构地区：[1]复旦大学研究生院,上海200032 [2]上海市肿瘤研究所细胞与分子免疫学研究室

出　　处：《中华肿瘤杂志》2005年第5期269-272,共4页Chinese Journal of Oncology

基　　金：上海市科学技术委员会资助项目(02ZB14090)

摘　　要：目的探讨小细胞肺癌(SCLC)抗独特型抗体3F6和其单链抗体(3F6ScFv)诱导体液和细胞免疫应答的能力,以证明其作为抗SCLC疫苗的可行性。方法3F6和3F6ScFv(Ab2)免疫BALB/c小鼠获得抗血清,以ELISA和Westernblot方法分别检测抗血清中Ab3结合SCLC细胞膜表面特异抗原(NCI H128抗原)的能力,用竞争Westernblot检测Ab3与2F7竞争结合NCI H128抗原的能力。以迟发型超敏反应(DTH反应)和小鼠脾脏淋巴细胞增殖实验检测3F6及3F6ScFv诱发细胞免疫应答的潜能。结果ELISA和Westernblot方法均证明,3F6和3F6ScFv免疫同系小鼠所产生的Ab3能特异的与NCI H128抗原相结合,与对照血清相比,差异有统计学意义(P<0.001),且有很强的与2F7(Ab1)竞争结合靶抗原的能力。在DTH反应中,3F6和3F6ScFv所致小鼠足垫肿胀的程度均明显高于对照组(P<0.001)。小鼠脾脏淋巴细胞增殖反应试验证明,用3F6和3F6ScFv免疫的小鼠脾脏淋巴细胞对靶细胞的再次刺激有明显的增殖反应,与阴性肿瘤细胞对照组和阴性抗体对照组相比,差异有统计学意义(P<0.05)。结论抗独特型抗体3F6和3F6ScFv均有模拟SCLC细胞膜表面特异抗原的能力,成功诱导了相应的体液和细胞免疫应答,可作为抗SCLC疫苗进行深入研究。Objective To investigate the efficacy of anti-idiotype antibody 3F6 and its single-chain variable fragment (3F6 ScFv) to induce humoral and cellular immune responses against small-cell-lung cancer(SCLC). Methods 3F6 and 3F6 ScFv (Ab2) were used to immunize BALB/c mice. The reaction of antibodies (Ab3) with specific antigen on NCI-H128 cells was tested by ELISA and Western blot, and the antibody binding inhibition assays were performed by competitive Western blot. Cellular immunity against SCLC induced by Ab2 was detected by a delayed-type hypersensitivity response and mouse lymphocyte proliferation assay. Results The sera immunized with Ab2 showed significant reaction (P<0.001, as compared to control sera) with SCLC-specific antigen on NCI-H128 cells and specifically competed the binding of 2F7 (Ab1) to the specific antigen. DTH responses challenged with NCI-H128 cells were significantly (P<0.001) stronger in mice immunized with Ab2 as compared to mice immunized with normal mouse IgG. T cell proliferation was significantly higher in Ab2-immunized mice (P<0.05) than in control mice. Conclusion The two kinds of anti-idiotypic antibodies successfully mimic the SCLC-specific antigen on NCI-H128 cell and induce strong humoral and cellular immune responses to SCLC-specific antigen in syngeneic mice. They may become novel vaccines against human small-cell-lung cancer and worthy of further investigation.

关 键 词：小细胞肺癌 抗独特型抗体 疫苗功能 试验研究 

分 类 号：R734.2[医药卫生—肿瘤] R392-33[医药卫生—临床医学]