Inhibitory anti-FGFR3 antibody is cytotoxic to t(4;14) multiple myeloma cells

07-19-2006

The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells.

According to scientists in Canada and 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 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," said Suzanne Trudel and collaborators at the University of Toronto in Canada and ProChon Biotech Ltd. in Israel. "The antibody inhibited the growth of FGFR3-expressing FDCP cells (IC50 of 0.5 mcg/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 growth of these cells," reported Trudel and her colleagues. "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," the authors concluded.

Trudel and her coauthors published their study in Blood (The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells. Blood, 2006;107(10):4039-4046).

For more information, contact Suzanne Trudel, Department of Medical Oncology, Princess Margaret Hospital, McLaughlin Center of Molecular Medicine, University of Toronto, 620 University Avenue, Room 8-204, Toronto, ON M5G 2C1, Canada. E-mail: strudel@uhnres.utoronto.ca.

Publisher contact information for the journal Blood is: American Society of Hematology, 1900 M Street NW, Suite 200, Washington, DC 20036, USA.

Keywords: Toronto, Ontario, Canada, Multiple Myeloma Therapy, Cancer Vaccine, Vaccine Development, Immunology, Immunotherapy, Monoclonal Antibody, Oncology, Proteomics.

This article was prepared by Cancer Vaccine Week editors from staff and other reports. Copyright 2006, Cancer Vaccine Week via NewsRx.com.