| Title | Construction, expression, and function of 6B11ScFv-mIL-12, a fusion protein that attacks human ovarian carcinoma |
| Authors | Cheng, Hongyan Ye, Xue Chang, Xiaohong Ma, Ruiqiong Cong, Xu Niu, Yidong Zhang, Menglei Liu, Kai Cui, Heng Sang, Jianli |
| Affiliation | Beijing Normal Univ, Coll Life Sci, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China. Peking Univ, Gynecol Oncol Ctr, Peoples Hosp, Beijing 100044, Peoples R China. Peking Univ, Gynecol Oncol Ctr, Peoples Hosp, 11 South Ave, Beijing 100044, Peoples R China. |
| Keywords | Ovarian cancer Anti-idiotypic antibody Interleukin-12 6B11 Fusion protein NON-HODGKINS-LYMPHOMA 1E10 ANTIIDIOTYPE VACCINE CELL LUNG-CANCER PHASE-I TRIAL MONOCLONAL-ANTIBODY CARCINOEMBRYONIC ANTIGEN ANTITUMOR-ACTIVITY COLORECTAL-CANCER DENDRITIC CELLS IMMUNE-RESPONSE |
| Issue Date | 2015 |
| Publisher | medical oncology |
| Citation | MEDICAL ONCOLOGY.2015,32,(4). |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/159665 |
| ISSN | 1357-0560 |
| DOI | 10.1007/s12032-015-0586-y |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
