卵巢癌抗独特型微抗体疫苗诱导BALB/c小鼠体内抗肿瘤免疫应答的实验研究  

In Vivo Study of Antitumor Immune Responses Induced by Anti idiotypic Minibody Vaccine of Ovarian Cancer

作　　者：昌晓红[1] 崔恒[1] 冯捷[1] 杨文兰[1] 李艺[1] 付天云[1] 

机构地区：[1]北京大学人民医院妇科肿瘤中心,北京100044

出　　处：《癌症》2004年第7期777-781,共5页Chinese Journal of Cancer

基　　金：国家高科技"863"基金资助项目(No.102-09-02-07);国家自然科学基金项目(No.30170978)~~

摘　　要：背景与目的6B11抗独特型微抗体由模拟人卵巢癌抗原的抗独特型单链抗体(6B11ScFv)融合人IgG1铰链区和CH3区所构成,它具有6B11ScFv和人IgGFc的双重免疫学活性。本研究观察6B11抗独特型微抗体在BALB/c小鼠体内诱导抗肿瘤免疫反应情况,探讨其作为卵巢癌疫苗的可能性。方法用卵巢癌6B11抗独特型微抗体免疫BALB/c小鼠。采用间接ELISA、竞争抑制实验和流式细胞术检测免疫鼠血清。结果6B11抗独特型微抗体免疫小鼠后,在不用佐剂的情况下可诱导小鼠产生较高的Ab3,末次免疫后30天仍持续在较高的水平。分别在末次免疫后4天、14天、24天和30天可刺激小鼠脾脏淋巴细胞CD4+T细胞和CD8+T细胞明显升高。结论6B11抗独特型微抗体可诱导机体产生特异体液免疫和细胞免疫反应,这为抗独特型微抗体疫苗的临床应用提供了一定的实验依据。BACKGROUND & OBJECTIVE: 6B11 anti idiotypic minibody can be constructed by fusion of anti idiotypic single chain antibody (6B11scFv) to human IgG1 hinge and CH3, which can simulate the function of ovarian carcinoma antigen. It has immune activity of both 6B11 and human immunoglobulin IgG1 Fc. This study was designed to evaluate whether anti tumor immune response can be induced in BALB/c mice immunized with 6B11anti idiotypic minibody and explore its probability as ovarian cancer vaccine. METHODS: BALB/c mice were immunized repeatedly by 6B11 anti idiotypic minibody. Competition inhibition test, indirect ELISA test, and immune flow cytometry were used for analyzing the serum characterization of anti anti idiotypic antibody (Ab3) and the changes of T lymphocyte phenotype of spleen. RESULTS: The specific antitumor immune response could be induced in BALB/c mice after immunized with anti idiotypic minibody without carrier proteins and adjuvant. The Ab3 maintained at a high level till 30 day after the last immunization. It stimulated proliferation of CD4+ T cells and CD8+ T cells from the spleen of BALB/c mice on 4th day, 14th day, 24th day, and 30th day after the last immunity respectively. CONCLUSIONS: 6B11 anti idiotypic minibody can induce both humoral and cellular immunity against ovarian carcinoma in vivo, which provided experimental evidence for clinical use of fusion protein 6B11 minibody as anti idiotype vaccines against ovarian carcinoma.

关 键 词：人卵巢癌 抗独特型微抗体 肿瘤疫苗 BALB/c小鼠 

分 类 号：R737.31[医药卫生—肿瘤]