Construction, expression, and function of 6B11ScFv–mIL-12, a fusion protein that attacks human ovarian carcinoma

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• 作者：Hongyan Cheng ; Xue Ye ; Xiaohong Chang ; Ruiqiong Ma ; Xu Cong ; Yidong Niu…
• 关键词：Ovarian cancer ; Anti ; idiotypic antibody ; Interleukin ; 12 ; 6B11 ; Fusion protein
• 刊名：Medical Oncology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：32
• 期：4
• 全文大小：1,278 KB
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• 刊物主题：Oncology; Hematology; Pathology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-131X

文摘

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?/sup>/CD56+ natural killer cells and CD3+/CD56+ natural killer T cells among peripheral lymphocytes, and increase interferon-γ. 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.