Fig. 1: Growth Kinetics of 5TGM1-luc in Immune-Competent C57BL/KaLwRij Mice by BLI
Fig. 2: Bioluminescent Imaging of 5TGM1 Cells in C57BL/KaLwRij Mice
The 5TGM1 multiple myeloma model arose spontaneously in aging C57BL/KaLwRij mice, and was propagated via serial passage in syngeneic mice prior to establishment of a cell line. Our 5TGM1 line has been luciferase-enabled to permit monitoring of growth in orthotopic sites such as the bone marrow by bioluminescent imaging (BLI). Intravenous implantation of 5TGM1-luc into syngeneic C57BL/KaLwRij mice results in progressive growth of the cells as monitored by BLI (Figure 1) with signal evident in the long bones (marrow) and other disseminated sites including lung, liver, spleen, spine, and brain (Figure 2). The 5TGM1-luc cells will also grow in an immune-deficient strain, the NIH-III Nude, aka beige nude xid, mouse with a more rapid time to evaluation of tumor burden in the bone.
Proteasome inhibitors have also become standard of care agents in the treatment of multiple myeloma. In the NIH-III mice, at the dose and regimen tested, the 5TGM1-luc model is completely non-responsive to carfilzomib (Figure 3a) by evaluation of whole body BLI; however, in the syngeneic setting, the 5TGM1-luc model shows a trend toward tumor growth delay (Figure 3b) that could be ideal for combination approaches.