Investigational New Drugs

, Volume 31, Issue 6, pp 1436–1443 | Cite as

OM-RCA-01, a novel humanized monoclonal antibody targeting fibroblast growth factor receptor 1, in renal cell carcinoma model

  • Ilya Tsimafeyeu
  • Elina Zaveleva
  • Evgenia Stepanova
  • Walter Low


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.


Fibroblast 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. 1.
    Tsimafeyeu I, Aksel E (2010) Renal cell carcinoma in the Russian federation in 2008. Malign Tumours 1:1–4Google Scholar
  2. 2.
    Posadas EM, Figlin RA (2012) Systemic therapy in renal cell carcinoma: advancing paradigms. Oncology (Williston Park) 26(3):290–301Google Scholar
  3. 3.
    Tsimafeyeu I, Demidov L, Stepanova E et al (2011) Overexpression of fibroblast growth factor receptors FGFR1 and FGFR2 in renal cell carcinoma. Scand J Urol Nephrol 45:190–195CrossRefPubMedGoogle Scholar
  4. 4.
    Rini BI, Atkins MB (2009) Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 10(10):992–1000CrossRefPubMedGoogle Scholar
  5. 5.
    Pal SK, Kortylewski M, Yu H, Figlin RA (2010) Breaking through a Plateau in renal cell carcinoma therapeutics: development and incorporation of biomarkers. Mol Cancer Ther 9(12):1–11CrossRefGoogle Scholar
  6. 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
  7. 7.
    Brochet X, Lefranc MP, Giudicelli V (2008) IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res 36:W503–W508PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Thompson JD, Higgins DG, Gibson TJ, Clustal W (1994) Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties, and weight matrix choice. Nucleic Acids Res 22:4673–4680PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Giudicelli V, Chaume D, Lefranc MP (2005) IMGT/GENE-DB : a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res 33:D256–D261PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Lefranc MP, Pommié C, Ruiz M et al (2003) IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol 27(1):55–77CrossRefPubMedGoogle Scholar
  11. 11.
    Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23:1147–1157CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ilya Tsimafeyeu
    • 1
  • Elina Zaveleva
    • 2
  • Evgenia Stepanova
    • 3
  • Walter Low
    • 4
  1. 1.Kidney Cancer Research BureauMoscowRussian Federation
  2. 2.OncoMax LtdMoscowRussian Federation
  3. 3.Laboratory of Tumor AngiogenesisN.N. Blokhin Russian Cancer Research CenterMoscowRussian Federation
  4. 4.PX’TherapeuticsGrenobleFrance

Personalised recommendations