http://scholars.nricm.edu.tw/handle/123456789/52
標題: | Chicken-derived humanized antibody targeting a novel epitope F2pep of fibroblast growth factor receptor 2: potential cancer therapeutic agent | 作者: | Tsai, Keng-Chang Chang, Chao-Di Cheng, Ming-Hui Lin, Tsai-Yu Lo, Yan-Ni Yang, Tz-Wen Chang, Fu-Ling Chiang, Chen-Wei Lee, Yu-Ching Yen, Yun |
公開日期: | 2019 | 期刊: | Acs Omega | 摘要: | Fibroblast growth factors (FGFs) and their receptors control various biological functions. Dysregulated FGF signaling has been implicated in the pathogenesis of human cancers. Aberrant activation of FGF receptor 2 (FGFR2) signaling caused by FGFR2 overexpression has been observed in various human cancers, such as gastric cancer. Antibodies are highly suitable for target therapy because of their specificity toward FGFR2. Patients with cancer and aberrantly activated FGFR2 signaling can benefit from therapeutic intervention with FGFR2-targeting antibodies. In this study, we produced the anti-FGFR2 single-chain variable fragment (scFv) from immunized chickens through the phage display method. The isolated scFv S3 targeted designed epitope F2pep of FGFR2 and prevented the access of FGFs; thus, it exhibited the ability to inhibit cell growth in gastric cancer. Furthermore, scFv S3 recognized endogenous FGFR2 on the cancer cells and inhibited downstream cell signaling. To study the inhibition effect of the humanized immunoglobulin G (IgG) hS3 in vivo, nonobese diabetic/severe combined immunodeficiency mice were inoculated with SUN16 cancer cells. An intravenous injection of hS3 inhibited tumor growth in the mice. Moreover, the hS3 also inhibited angiogenesis in the matrix gel-assisted angiogenesis model. After using site-directed mutagenesis to identify the key residue on the hS3-targeting site of FGFR2, molecular modeling was used to determine the interaction between hS3 and FGFR2. Rational molecular docking analysis results revealed that two ionic interactions caused the interaction between scFv hS3 and the peptide F2pep of FGFR2. The results showed that antibody hS3 has high potential in cancer therapy in the future. | 描述: | Acs Omega 4(1): 2387-2397 | URI: | http://localhost/handle/123456789/52 | DOI: | 10.1021/acsomega.8b03072 |
顯示於: | 張芳榮 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。