title: OM-RCA-01, a novel humanized monoclonal antibody targeting fibroblast growth factor receptor 1, in renal cell carcinoma model.
abstract: Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic target for treatment of metastatic renal cell carcinoma (RCC). We investigated the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1 antibody in RCC. OM-RCA-01 has been shown to inhibit in vitro kinase activity of FGFR1 and has high affinity (Kd of 1.59 nM). In human renal carcinoma Caki-1 FGFR1-expressing cells, OM-RCA-01 potently inhibited FGF-mediated signaling and proliferation. In vivo, the tumors in untreated mice or mice treated with non-specific IgG continued their aggressive growth to reach the size of 2,000 cm3, at which point the mice were killed. In contrast, treatment with OM-RCA-01 not only significant arrested further growth of the tumors (P < 0.01) but also demonstrated differences in tumor volume compared with vehicle already on Day 13. A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was given in low (1 mg/kg) or high (10 mg/kg) doses (P = 0.917). In Matrigel assay, OM-RCA-01 significantly inhibited FGF-induced endothelial cell migration, capillary-like tubular structure and mature vessels formation. Administration of 10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no observations of gross toxicity were made. Collectively, the data obtained with OM-RCA-01 are consistent with potent inhibition of FGFR1-signaling, angiogenesis, and tumor growth. OM-RCA-01 is being developed clinically as an intravenous therapy for the treatment of clear cell RCC.
authors.affiliation: Kidney Cancer Research Bureau, Bazovskaya ul. 4/1-15, Moscow, 125635, Russian Federation, tsimafeyeu@gmail.com.
authors.forename: Ilya
authors.initials: I
authors.lastname: Tsimafeyeu
authors.forename: Elina
authors.initials: E
authors.lastname: Zaveleva
authors.forename: Evgenia
authors.initials: E
authors.lastname: Stepanova
authors.forename: Walter
authors.initials: W
authors.lastname: Low
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D051496:Receptor, Fibroblast Growth Factor, Type 1
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