Anti-tumor and anti-angiogenic effects of Aplidin in the 5T33MM, syngeneic, model of multiple myeloma .

In vivo, chronic treatment with Aplidin was well tolerated and reduced serum paraprotein concentration with 42% (p<0,001) while BM invasion with myeloma cells was decreased with 35% (p<0,001). Next to directly affect myeloma cells, Aplidin also reduced the myeloma associated neo-vascularization to basal values. This anti-angiogenic effect was confirmed in vitro using a BM endothelial cell line and a Rat Aortic Ring Assay in which Aplidin inhibited cell proliferation and vessel formation in MM induced neovascularization. These data indicate that Aplidin is well tolerated in vivo and its anti-tumor and anti-angiogenic effects support the use of the drug in chronic dosing schedules of multiple myeloma.