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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4039-4046. Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-10-4179. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4179v1 107/10/4039    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Trudel, S. Articles by Yayon, A. Search for Related Content PubMed PubMed Citation Articles by Trudel, S. Articles by Yayon, A. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells Suzanne Trudel, A. Keith Stewart, Eran Rom, Ellen Wei, Zhi Hua Li, Sarit Kotzer, Irina Chumakov, Yossi Singer, Hong Chang, Sheng-Ben Liang, and Avner Yayon From the Department of Medical Oncology, Princess Margaret Hospital and McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, ON, Canada; and ProChon Biotech Ltd, Rehovot, Israel. The association of fibroblast growth factor receptor 3 (FGFR3) expression with t(4;14) multiple myeloma (MM) and the demonstration of the transforming potential of this receptor tyrosine kinase (RTK) make it a particularly attractive target for drug development. We report here a novel and highly specific anti-FGFR3–neutralizing antibody (PRO-001). PRO-001 binds to FGFR3 expressed on transformed cells and inhibits FGFR3 autophosphorylation and downstream signaling. The antibody inhibited the growth of FGFR3-expressing FDCP cells (IC50 of 0.5 µg/mL) but not that of cells expressing FGFR1 or FGFR2, and potently inhibited FGFR3-dependent solid tumor growth in a mouse xenograft model. Furthermore, PRO-001 inhibited the growth of the FGFR3-expressing, human myeloma cell line, UTMC2. Inhibition of viability was still observed when cells were cocultured with stroma or in the presence of IL-6 or IGF-1. PRO-001 did not inhibit constitutive activation of K650E, G384D, and Y373C FGFR3 in myeloma cell lines and failed to inhibit the growth of these cells. Most importantly, however, PRO-001 induced cytotoxic responses in primary t(4;14)+ MM samples with an increase in apoptotic index of 20% to 80% as determined by annexin V staining. The data demonstrate that PRO-001 is a potent and specific inhibitor of FGFR3 and deserves further study for the treatment of FGFR3-expressing myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Salazar, T. Kashiwada, P. Krejci, P. Muchowski, D. Donoghue, W. R. Wilcox, and L. M. Thompson A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells Hum. Mol. Genet., June 1, 2009; 18(11): 1951 - 1961. [Abstract] [Full Text] [PDF] D. C. Tomlinson, F. R. Lamont, S. D. Shnyder, and M. A. Knowles Fibroblast Growth Factor Receptor 1 Promotes Proliferation and Survival via Activation of the Mitogen-Activated Protein Kinase Pathway in Bladder Cancer Cancer Res., June 1, 2009; 69(11): 4613 - 4620. [Abstract] [Full Text] [PDF] J. Yang, Y. Cao, S. Hong, H. Li, J. Qian, L. W. Kwak, and Q. Yi Human-Like Mouse Models for Testing the Efficacy and Safety of Anti-{beta}2-Microglobulin Monoclonal Antibodies to Treat Myeloma Clin. Cancer Res., February 1, 2009; 15(3): 951 - 959. [Abstract] [Full Text] [PDF] G. Bisping, D. Wenning, M. Kropff, D. Gustavus, C. Muller-Tidow, M. Stelljes, G. Munzert, F. Hilberg, G. J. Roth, M. Stefanic, et al. Bortezomib, Dexamethasone, and Fibroblast Growth Factor Receptor 3-Specific Tyrosine Kinase Inhibitor in t(4;14) Myeloma Clin. Cancer Res., January 15, 2009; 15(2): 520 - 531. [Abstract] [Full Text] [PDF] J Yeung and H Chang Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma J. Clin. Pathol., July 1, 2008; 61(7): 832 - 836. [Abstract] [Full Text] [PDF] J. San-Miguel, J.-L. Harousseau, D. Joshua, and K. C. Anderson Individualizing Treatment of Patients With Myeloma in the Era of Novel Agents J. Clin. Oncol., June 1, 2008; 26(16): 2761 - 2766. [Abstract] [Full Text] [PDF] S. R. Moore, D. L. Persons, J. A. Sosman, D. Bobadilla, V. Bedell, D. D. Smith, S. R. Wolman, R. J. Tuthill, J. Moon, V. K. Sondak, et al. Detection of Copy Number Alterations in Metastatic Melanoma by a DNA Fluorescence In situ Hybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431) Clin. Cancer Res., May 15, 2008; 14(10): 2927 - 2935. [Abstract] [Full Text] [PDF] J. L. Martinez-Torrecuadrada, L. H. Cheung, P. Lopez-Serra, R. Barderas, M. Canamero, S. Ferreiro, M. G. Rosenblum, and J. I. Casal Antitumor activity of fibroblast growth factor receptor 3-specific immunotoxins in a xenograft mouse model of bladder carcinoma is mediated by apoptosis Mol. Cancer Ther., April 1, 2008; 7(4): 862 - 873. [Abstract] [Full Text] [PDF] S. V. Sharma and J. Settleman Oncogene addiction: setting the stage for molecularly targeted cancer therapy Genes & Dev., December 15, 2007; 21(24): 3214 - 3231. [Abstract] [Full Text] [PDF] R. Z. 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