title: Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies.
abstract: BACKGROUND
  The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy.
  
  
  METHODS
  Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs.
  
  
  RESULTS
  These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice.
  
  
  CONCLUSIONS
  These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.
authors.affiliation: Pfizer Global Research and Development, St Louis, Missouri, USA. Herbert.A.Runnels@pfizer.com
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Runnels
authors.forename: J Alan
authors.initials: JA
authors.lastname: Arbuckle
authors.forename: Karen S
authors.initials: KS
authors.lastname: Bailey
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nicastro
authors.forename: Duo
authors.initials: D
authors.lastname: Sun
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Pegg
authors.forename: Debra M
authors.initials: DM
authors.lastname: Meyer
authors.forename: Michelle
authors.initials: M
authors.lastname: Evans
authors.forename: Christine P
authors.initials: CP
authors.lastname: Bono
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Lie
authors.forename: Mark A
authors.initials: MA
authors.lastname: Moffat
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Casperson
authors.forename: Simon
authors.initials: S
authors.lastname: Lennard
authors.forename: John
authors.initials: J
authors.lastname: Elvin
authors.forename: Tristan
authors.initials: T
authors.lastname: Vaughan
authors.forename: Christine E
authors.initials: CE
authors.lastname: Smith
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Morton
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000915:Antibody Affinity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D018604:Epitope Mapping; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017526:Receptor, IGF Type 1 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D017526:Receptor, IGF Type 1