In vitro suppression of leukemia by alkylated interleukin-3

We report the in vitro suppression of the IL-3-dependent MO-7 acute myeloid leukemia proliferation by an interleukin-3 antagonist. The antagonist was generated by alkylation to inactivate catalytic His-residues of native human interleukin-3. The resulting inhibitor caused a factor 7 inhibition of the growth-response curve of the IL-3 control-stimulated proliferation of a MO-7 leukemia cell line. A 40% inhibition of the MO-7 proliferation could be achieved with a partially alkylated inhibitor in presence of a factor 30 excess of native IL-3. Therefore, the inhibitor had a substantially improved affinity for the IL-3 receptor on these leukemia cells. At a concentration of as low as 0.1 ng/ml it still caused a 2-fold inhibition of the native IL-3-stimulated proliferation response curve. Thus it can be concluded that this alkylate IL-3 is a potent IL-3 antagonist. Based on the reported specific zinc binding of IL-2, IL-6, GM-CSF and gamma-interferon this suggests that more leukemias and even other forms of cancer can be effectively suppressed by alkylated growth factors.