期刊
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
卷 46, 期 -, 页码 1082-1090出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/21691401.2018.1478846
关键词
Phage display; Antibody fragment; Glycine-extended gastrin 17; Colorectal cancer
资金
- Research Center for Pharmaceutical Nanotechnology (RCPN) [95003]
Glycine-extended gastrin 17 (G17-Gly), a dominant processing intermediate of gastrin gene, has been implicated in the development or maintenance of colorectal cancers (CRCs). Hence, neutralizing G17-Gly activity by antibody entities can provide a potential therapeutic strategy in the patients with CRCs. To this end, we isolated fully human antibody fragments from a phage antibody library through biopanning against different epitopes of G17-Gly in order to obtain the highest possible antibody diversity. ELISA screening and sequence analysis identified 2 scFvs and 4 V-L antibody fragments. Kinetic analysis of the antibody fragments by SPR revealed K-D values to be in the nanomolar range (87.9-334nM). The selected anti-G17-Gly antibody fragments were analyzed for growth inhibition and apoptotic assays in a CRC cell line, HCT-116, which is well-characterized for expressing gastrin intermediate species but not amidated gastrin. The antibody fragments exhibited significant inhibition of HCT-116 cells proliferation ranging from 36.5 to 73% of controls. Further, Annexin V/PI staining indicated that apoptosis rates of scFv H8 and V-L G8 treated cells were 45.8 and 63%, respectively. Based on these results, we for the first time, demonstrated the isolation of anti-G17-Gly human scFv and V-L antibodies with potential therapeutic applications in G17-Gly-responsive tumors.
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