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学科主题: 临床医学
题名:
Construction, expression, and function of 6B11ScFv-mIL-12, a fusion protein that attacks human ovarian carcinoma
作者: Cheng, Hongyan1,2; Ye, Xue2; Chang, Xiaohong2; Ma, Ruiqiong2; Cong, Xu2; Niu, Yidong2; Zhang, Menglei2; Liu, Kai2; Cui, Heng2; Sang, Jianli1
关键词: Ovarian cancer ; Anti-idiotypic antibody ; Interleukin-12 ; 6B11 ; Fusion protein
刊名: MEDICAL ONCOLOGY
发表日期: 2015-04-01
DOI: 10.1007/s12032-015-0586-y
卷: 32, 期:4
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: NON-HODGKINS-LYMPHOMA ; 1E10 ANTIIDIOTYPE VACCINE ; CELL LUNG-CANCER ; PHASE-I TRIAL ; MONOCLONAL-ANTIBODY ; CARCINOEMBRYONIC ANTIGEN ; ANTITUMOR-ACTIVITY ; COLORECTAL-CANCER ; DENDRITIC CELLS ; IMMUNE-RESPONSE
英文摘要:

We previously produced an anti-idiotypic monoclonal antibody, 6B11, which mimics ovarian cancer antigen CA166-9 and induces cellular and humoral immunity. Here, to enhance the immunogenicity of 6B11, we constructed the 6B11ScFv-mIL-12 fusion protein (FP), by fusing single-chain fragment of 6B11 variable region (6B11ScFv) with mouse interleukin-12 (mIL-12), which was expressed in eukaryotic 293EBNA cells transfected with pSBI vectors. A binding activity assay showed 6B11ScFv-mIL-12 to have activities of both 6B11 and mIL-12-it specifically bound both ovarian monoclonal antibody COC166-9 and rabbit anti-mouse IL-12 antibody. The immune activity assay showed 6B11ScFv-mIL-12 to promote proliferation of lymphocytes stimulated by phytohemagglutinin, increase the absolute numbers and percentages of CD3(-)/CD56(+) natural killer cells and CD3(+)/CD56(+) natural killer T cells among peripheral lymphocytes, and increase interferon-gamma. The FP was specifically cytotoxic to the CA166-9(+) ovarian cancer cell lines HOC1A and SKOV3 and inhibited growth of ID8 subcutaneous tumors in C57BL/6J mice. This study provides an experimental basis for clinical use of 6B11ScFv-mIL-12 in ovarian cancer therapy. To our knowledge, this is the first report of a fusion protein from an anti-idiotypic antibody and IL-12.

语种: 英语
所属项目编号: 30901748 ; 2012AA02A507
项目资助者: National Natural Science Foundation of China (NSFC) ; National High Technology Research and Development Program (863 Program)
WOS记录号: WOS:000351474100044
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57537
Appears in Collections:北京大学第二临床医学院_妇科肿瘤中心_期刊论文

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作者单位: 1.Beijing Normal Univ, Coll Life Sci, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China
2.Peking Univ, Gynecol Oncol Ctr, Peoples Hosp, Beijing 100044, Peoples R China

Recommended Citation:
Cheng, Hongyan,Ye, Xue,Chang, Xiaohong,et al. Construction, expression, and function of 6B11ScFv-mIL-12, a fusion protein that attacks human ovarian carcinoma[J]. MEDICAL ONCOLOGY,2015,32(4).
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