title: Monoclonal antibodies to fibroblast growth factor receptor 2 effectively inhibit growth of gastric tumor xenografts.
abstract: OBJECTIVE
  Overexpression of fibroblast growth factor receptor 2 (FGFR2) may be a causative factor of a number of human tumors, especially gastric tumors of the poorly differentiated type. We investigated whether monoclonal antibodies (mAbs) directed against FGFR2 can inhibit the growth of tumors in xenograft models.
  
  
  METHODS
  We generated and characterized 3 mAbs that recognize different epitopes on FGFR2: GAL-FR21, GAL-FR22, and GAL-FR23. The ability of the mAbs to recognize the FGFR2IIIb and FGFR2IIIc isoforms of FGFR2 was determined, as was their ability to block binding of FGF ligands to FGFR2. The capability of the mAbs to inhibit FGF-induced FGFR2 phosphorylation and to downmodulate FGFR2 expression was also investigated. Finally, the ability of the anti-FGFR2 mAbs to inhibit tumor growth was determined by establishing xenografts of SNU-16 and OCUM-2M human gastric tumor cell lines in nude mice, treating with each mAb (0.5-5 mg/kg intraperitoneally twice weekly) and monitoring tumor size.
  
  
  RESULTS
  Of the 3 mAbs, GAL-FR21 binds only the FGFR2IIIb isoform, whereas GAL-FR22 and GAL-FR23 bind to both the FGFR2IIIb and FGFR2IIIc forms, with binding regions respectively in the D3, D2-D3, and D1 domains of FGFR2. GAL-FR21 and GAL-FR22 blocked the binding of FGF2, FGF7 and FGF10 to FGFR2IIIb. GAL-FR21 inhibited FGF2 and FGF7 induced phosphorylation of FGFR2, and both mAbs downmodulated FGFR2 expression on SNU-16 cells. These mAbs effectively inhibited growth of established SNU-16 and OCUM-2M xenografts in mice.
  
  
  CONCLUSIONS
  Anti-FGFR2 mAbs GAL-FR21 and GAL-FR22 have potential for the treatment of gastric and other tumors.
authors.affiliation: Galaxy Biotech, LLC, Sunnyvale, California 94089, USA.
authors.forename: Wei-meng
authors.initials: WM
authors.lastname: Zhao
authors.forename: Lihong
authors.initials: L
authors.lastname: Wang
authors.forename: Hangil
authors.initials: H
authors.lastname: Park
authors.forename: Sophea
authors.initials: S
authors.lastname: Chhim
authors.forename: Melanie
authors.initials: M
authors.lastname: Tanphanich
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: K Jin
authors.initials: KJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D051497:Receptor, Fibroblast Growth Factor, Type 2