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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF.

We have previously demonstrated that diphtheria toxin (DT) fused to human GM-CSF effectively eliminates human long-term leukemia initiating cells in SCID mice. However, because huGM-CSF does not react with the murine GM-CSF receptor possible side-effects to nonleukemic tissues could not be analyzed in the AML/SCID model. To overcome this problem, we used murine GM-CSF fused to DT and studied the therapeutic index in the rat leukemia model BNML/LT12. In DT-mGM-CSF dose escalation experiments, severe dose-dependent toxicity to organs such as liver, kidney and lung was observed. Therefore, the antileukemic effects were evaluated with the lower doses. Daily intraperitoneal bolus injections of 75 microg/kg/day for 7 days induced a 3 log leukemic cell kill. The dose of 75 microg/kg/day had no effect on the hemopoietic progenitor cell subsets. These in vivo studies show that the DT-GM-CSF fusion protein can be used for specifically targeting leukemic cells and thus has potential as a therapeutic agent in the treatment of AML.[1]


  1. In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF. Rozemuller, H., Rombouts, E.J., Touw, I.P., FitzGerald, D.J., Kreitman, R.J., Hagenbeek, A., Martens, A.C. Leukemia (1998) [Pubmed]
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