|
|
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.
 Previous Article | Next Article 
Submitted October 21, 2005
Accepted December 31, 2005
The inhibitory anti-FGFR3 antibody, PRO-001 is cytotoxic to t(4;14) multiple myeloma cells
Suzanne Trudel*, A K Stewart, Eran Rom, Ellen Wei, Zhi Hua Li, Sarit Kotzer, Irina Chumakov, Yossi Singer, Hong Chang, Sheng-Ben Liang, and Avner Yayon
Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ont., Canada; McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Ont., Canada
Prochon Biotech Ltd., Rohovot, Israel
Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ont., Canada
* Corresponding author; email: strudel{at}uhnres.utoronto.ca.
The association of 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 FCDP cells (IC50 of 0.5µg/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 co-cultured 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) positive MM samples with an increase in apoptotic index of 20-80% as determined by annexin V staining. The data demonstrates 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:
|
|
|
|
 
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. Orlowski
Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation
Hematology,
January 1, 2006;
2006(1):
338 - 347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
