SCID mouse model enables rapid evaluation of treatments for multiple myeloma

08-14-2006

A severe combined immunodeficient mouse model enables rapid evaluation of treatments for multiple myeloma.

According to recent research published in the International Journal of Oncology, "We set out to generate new human myeloma tumors that grow in immunodeficient mice and can be used for pathophysiological studies and rapid evaluation of new therapies. Fresh whole core bone marrow (BM) biopsies taken from 33 myeloma patients were engrafted into the hind limb muscle of severe combined immunodeficient (SCID) mice."

"Human Ig was detected in 28/33 mice and three grew palpable tumors displaying many features of human myeloma including morphology, immunophenotype and BM plasmacytosis. Following intramuscular passage, we generated large numbers of mice with predictable increases in tumor growth and human paraprotein levels," scientists reported.

"We further characterized the model generated from an IgG lambda-producing tumor known as LAG lambda-1 and determined the effects of the proteasome inhibitor bortezomib, the alkylating agent melphalan, and the DNA damaging agent liposomal doxorubicin, on the growth of this tumor.

"LAG lambda-1-bearing mice receiving higher doses of bortezomib showed reduced tumor growth whereas a lower dose had no effect. In contrast," said R.A. Campbell and colleagues at the Institute for Myeloma & Bone Cancer Research in West Hollywood, "melphalan did not significantly alter tumor growth, except minimally at high doses, reflecting the resistance of this patient's tumor to this drug."

"We also used our intramuscular (i.m.) LAG lambda-1 model to optimize the dosing schedule of liposomal doxorubicin. Low doses administered once daily 3 days per week decreased tumor growth and human paraprotein levels whereas much higher doses given once weekly had no antimyeloma effects.

"Furthermore," continued the authors, "LAG lambda-1 cells produce local tumors when injected subcutaneously and lytic lesions when injected intravenously allowing for multiple methods of evaluating the antimyeloma effects of a variety of agents."

Campbell concluded, "Our new clinically relevant SCID models of human myeloma should greatly facilitate drug development and enable novel therapies to quickly move from the laboratory to the clinic."

Campbell and colleagues published their study in International Journal of Oncology (LAG lambda-1: A clinically relevant drug resistant human multiple myeloma tumor murine model that enables rapid evaluation of treatments for multiple myeloma. Int J Oncol, 2006;28(6):1409-1417).

For additional information, contact J.R. Berenson, Institute Myeloma & Bone Cancer Research, Suite 300, 9201 Sunset Blvd., W Hollywood, CA 90069, USA.

The publisher's contact information for the International Journal of Oncology is: Professor D a Spandidos, 1, S Merkouri St., Editorial Office, Athens 116 35, Greece.

Keywords: West Hollywood, California, United States, Drug Development, Multiple Myeloma, SCID Mouse, LAG Lambda-1 Cells, Anticancer Therapy.

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