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Blood, 15 July 2005, Vol. 106, No. 2, pp. 713-716.
Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2005-01-0373.
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Submitted February 9, 2005
Accepted March 3, 2005
A clinically relevant SCID-hu in vivo model of human multiple myeloma
Pierfrancesco Tassone, Paola Neri, Daniel R Carrasco, Renate Burger, Victor S Goldmacher, Robert Fram, Vidit Munshi, Laurence Catley, Gary S Jacob, Salvatore Venuta, Kenneth C Anderson, and Nikhil C Munshi*
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA; University of 'Magna Graecia', Catanzaro, Italy
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA
ImmunoGen, Inc., Cambridge, MA, USA
VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA
Callisto Pharmaceuticals Inc., New York, NY, USA
University of 'Magna Graecia', Catanzaro, Italy
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA
* Corresponding author; email: Nikhil_Munshi{at}dfci.harvard.edu.
We developed a novel in vivo multiple myeloma (MM) model by engrafting the IL-6-dependent human MM cell line INA-6 into SCID mice previously transplanted with a human fetal bone chip (SCID-hu mice). INA-6 cells require either exogenous human IL-6 (huIL-6) or bone marrow stromal cells (BMSCs) to proliferate in vitro. In this model, we monitored the in vivo growth of INA-6 cells stably transduced with a green fluorescent protein gene (INA-6GFP+ cells). INA-6 MM cells engrafted in SCID-hu mice, but not in SCID mice that had not been implanted with human fetal bone. The level of soluble human IL-6 receptor (shuIL-6R) in serum and fluorescence imaging of host animals were sensitive indicators of tumor growth. Dexamethasone as well as experimental drugs, such as Atiprimod and B-B4-DM1, were used to confirm the utility of the model for evaluation of anti-MM agents. We report that this model is highly reproducible and allows for evaluation of investigational drugs targeting IL-6 dependent MM cells in the human bone marrow (huBM) milieu.

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