The efficacy of diphtheria-growth factor fusion proteins is enhanced by co-administration of cytosine arabinoside in an immunodeficient mouse model of human acute myeloid leukemia.
Addition of cytosine arabinoside (Ara-C) to truncated diphtheria toxin (DT388) fused to granulocyte macrophage-colony stimulating factor (GMCSF) or interleukin-3 (IL3) was studied in a NOD/SCID mouse model of human AML. Ara-C alone did not reduce the % human AML cells in mouse bone marrow (BM). DT388IL3 or DT388GMCSF alone reduced but did not eradicate engraftment for two of four and two of three samples, respectively. In contrast, Ara-C with DT388IL3 eliminated AML from mouse BM with one of four samples while DT388GMCSF with Ara-C eliminated or reduced AML cells as compared to mice receiving either agent alone with two of three samples.
Hogge
Donna E
DE
Terry Fox Laboratory, British Columbia Cancer Agency, 601 West 10th Avenue, Vancouver, Canada V5Z 1L3. dhogge@bccancer.bc.ca
Feuring-Buske
Michaela
M
Gerhard
Brigitte
B
Frankel
Arthur E
AE
D000818:Animals; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*
D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor