OM-RCA-01, a novel humanized monoclonal antibody targeting fibroblast growth factor receptor 1, in renal cell carcinoma model
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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.
KeywordsFibroblast growth factors Fibroblast growth factor receptors FGFR1 antibody OM-RCA-01 Renal cell carcinoma Anti-tumor activity
We would like to thank Maxwell Biotech, RVC and Skolkovo Funds for grant support.
IT, ES, and WL received research funding from OncoMax Ltd. EZ is a former employee of OncoMax Ltd.
- 1.Tsimafeyeu I, Aksel E (2010) Renal cell carcinoma in the Russian federation in 2008. Malign Tumours 1:1–4Google Scholar
- 2.Posadas EM, Figlin RA (2012) Systemic therapy in renal cell carcinoma: advancing paradigms. Oncology (Williston Park) 26(3):290–301Google Scholar
- 6.Tsimafeyeu I, Demidov L, Ta H, Stepanova E, Wynn N (2010) Fibroblast growth factor pathway in renal cell carcinoma. J Clin Oncol (Meeting Abstr) 28(15Suppl):4621Google Scholar