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

Cytotoxicity of anti-CD64-ricin a chain immunotoxin against human acute myeloid leukemia cells in vitro and in SCID mice.

Blast cells from patients with acute myeloid leukemia ( AML) commonly express CD64, the high-affinity receptor for immunoglobulin G (FcgammaRI). An immunotoxin (MDX-44) was constructed by coupling humanized anti-CD64 monoclonal antibody (mAb) H22 via a bivalent linker to deglycosylated ricin A-chain (RA). Human leukemia cell lines were incubated with MDX-44 or H22/free RA. The effect of MDX-44 on the proliferation of leukemia cells was assessed by [(3)H]thymidine incorporation. In the presence of interferon-gamma ( IFN-gamma), MDX-44 significantly inhibited the proliferation of CD64(+) HL-60, NB4, and U937 cells in 72-h cultures in a dose-dependent manner. The mechanism of action appeared to be the induction of apoptosis, as measured by propidium iodide staining and flow cytometry analysis. However, CD64(-) KG-1a and Daudi cells were not affected by MDX-44/ IFN-gamma. Incubating HL-60 cells with MDX-44/ IFN-gamma resulted in a 99% decrease in colony-forming units, whereas colony-forming cells in normal bone marrow were not significantly suppressed by such treatment. Cells from 60% of AML patients (6/10) were inhibited by MDX-44/ IFN-gamma, and the inhibition was correlated with CD64 expression on these cells (r = 0.65). In a human AML model in NOD/SCID mice, MDX-44/ IFN-gamma inhibited 95-98% of peritoneal exudate AML cell proliferation and 85-90% of solid leukemia masses. The effect of MDX-44 on AML cells was dependent on activation of cells by IFN-gamma. MDX-44/ IFN-gamma may have value in the therapy of AML cells expressing cell-surface CD64.[1]

References

  1. Cytotoxicity of anti-CD64-ricin a chain immunotoxin against human acute myeloid leukemia cells in vitro and in SCID mice. Zhong, R.K., van de Winkel, J.G., Thepen, T., Schultz, L.D., Ball, E.D. J. Hematother. Stem Cell Res. (2001) [Pubmed]
 
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