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Humoral immune responses induced by anti-idiotypic antibody fusion protein of 6B11scFv/hGM-CSF in BALB/c mice
作者姓名:CHANG  Xiao-hong  YE  Xue  CUI  Heng  FENG  Jie  LI  Yi  ZHU  Hong-lan  YANG  Wen-lan  FU  Tian-yun  CHENG  Hong-yan  GUO  Hui-fang
作者单位:Gynecologic Oncology Center, Peking University People's Hospital, Beijing 100044, China
基金项目:This study was supported by a grant from the National Natural Science Foundation of China (No. 30471959 and 30571940).
摘    要:Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B 11, which mimics an ovarian carcinoma associated antigen OC166-9 and whose corresponding monoclonal antibody is COC166-9 (Abl). In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment (scFv)/human granulocyte macrophage colony-stimulating factor (hGM-CSF) and 6B 1 lscFv in BALB/c mice. Methods The fusion protein 6B 11 scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSE BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. Results The fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F(ab)2' and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6BllScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11 scFv/hGM-CSF compared with the 6B11 scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. Conclusion The fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11 scFv/hGM-CSF for active immunotherapy of ovarian cancer.

关 键 词:体液免疫  抗体蛋白  6B11scFv/hGM-CSF  BALB/c  小鼠  动物实验
收稿时间:2005-09-22

Humoral immune responses induced by anti-idiotypic antibody fusion protein of 6B11scFv/hGM-CSF in BALB/c mice
CHANG Xiao-hong YE Xue CUI Heng FENG Jie LI Yi ZHU Hong-lan YANG Wen-lan FU Tian-yun CHENG Hong-yan GUO Hui-fang.Humoral immune responses induced by anti-idiotypic antibody fusion protein of 6B11scFv/hGM-CSF in BALB/c mice[J].Chinese Medical Journal,2006,19(2):131-139.
Authors:CHANG Xiao-hong  YE Xue  CUI Heng  FENG Jie  LI Yi  ZHU Hong-lan  YANG Wen-lan  FU Tian-yun  CHENG Hong-yan  GUO Hui-fang
Abstract:Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B11, which mimics an ovarian carcinoma associated antigen OC166-9 and whose corresponding monoclonal antibody is COC166-9 (Ab1). In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment (scFv)/human granulocyte macrophage colony-stimulating factor (hGM-CSF) and 6B11scFv in BALB/c mice. Methods The fusion protein 6B11scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSF. BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. Results The fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F(ab)2' and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6B11ScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11scFv/hGM-CSF compared with the 6B11scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. Conclusion The fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11scFv/hGM-CSF for active immunotherapy of ovarian cancer.
Keywords:anti-idiotypic antibody  ovarian carcinoma  recombinant fusion protein  humoral immune responses  BALB/c mice
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