title: A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts.
abstract: The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer.
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Rui
authors.affiliation: Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: srrshurology@163.com.
authors.forename: Zhigen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: C-Met; Hepatocyte growth factor (HGF); Prostate cancer; Rabbit monoclonal antibody