Chang Xiao-Hong, Cui Heng, Feng Jie, Yang Wen-Lan, Li Yi, Fu Tian-Yun
Gynecologic Oncology Center, Peking University People's Hospital, Beijing, 100044, P.R.China.
Ai Zheng. 2004 Jul;23(7):777-81.
BACKGROUND & OBJECTIVE: 6B11 anti-idiotypic minibody can be constructed by fusion of anti-idiotypic single chain antibody (6B11scFv) to human IgG(1) hinge and CH3, which can simulate the function of ovarian carcinoma antigen. It has immune activity of both 6B11 and human immunoglobulin IgG(1) 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.
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.
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.
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.
抗独特型微抗体6B11可通过将抗独特型单链抗体(6B11scFv)与人IgG(1)铰链区和CH3融合构建而成,其可模拟卵巢癌抗原的功能。它具有6B11和人免疫球蛋白IgG(1) Fc的免疫活性。本研究旨在评估用6B11抗独特型微抗体免疫BALB/c小鼠是否能诱导抗肿瘤免疫反应,并探讨其作为卵巢癌疫苗的可能性。
用6B11抗独特型微抗体反复免疫BALB/c小鼠。采用竞争抑制试验、间接ELISA试验和免疫流式细胞术分析抗抗独特型抗体(Ab3)的血清特性及脾脏T淋巴细胞表型的变化。
用无载体蛋白和佐剂的抗独特型微抗体免疫BALB/c小鼠后可诱导特异性抗肿瘤免疫反应。Ab3在末次免疫后30天内维持在高水平。末次免疫后第4天、第14天、第24天和第30天分别刺激BALB/c小鼠脾脏中CD4+ T细胞和CD8+ T细胞增殖。
6B11抗独特型微抗体可在体内诱导针对卵巢癌的体液免疫和细胞免疫,为融合蛋白6B11微抗体作为卵巢癌抗独特型疫苗的临床应用提供了实验依据。