title: Initial testing (Stage 1) of TAK-701, a humanized hepatocyte growth factor binding antibody, by the Pediatric Preclinical Testing Program.
abstract: TAK-701 is a humanized antibody that binds hepatocyte growth factor (HGF), thus suppressing c-Met transduced signaling and c-Met dependent proliferation and migration of tumor cells. Six childhood solid tumor xenografts were selected for evaluating TAK-701 based on immunochemical detection of HGF/c-Met autocrine signaling [i.e., pMet(Tyr1349) and HGF positive]. TAK-701 was tested using a dose of 30 mg/kg administered by the intraperitoneal (IP) route twice weekly for 4 weeks. TAK-701 did not induce significant differences in EFS distribution in treated tumors compared to control tumors. Objective responses were not observed in any of the tested solid tumor xenografts.
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: c-Met inhibition; developmental therapeutics; preclinical testing
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