Effects of low-dose mafosfamid on the lymphokine-activated killer cell activity of peripheral blood mononuclear cells determined by a clonogenic microassay

Abstract

The effects of mafosfamid on lymphokine-activated killer (LAK) cells were examined, using a newly developed clonogenic microassay with tumor target cells instead of the common 51Cr release. When nonadherent peripheral blood mononuclear effector cells were exposed to 1 x 10(-9) or 1 x 10(-8) M mafosfamid 1 h prior to activation with interleukin 2 (IL-2), LAK-cell activity increased, resulting in fewer colonies of human KB squamous carcinoma cells than without mafosfamid treatment. In contrast, when effector cells were exposed to mafosfamid after IL-2 activation LAK-cell activity was inhibited. Notably, the in vitro immunomodulatory effects of mafosfamid were detected at concentrations 100-1000 times below those shown to be cytotoxic. Although the mechanisms remain to be elucidated, our results might be an in vitro representation of the known in vivo immunostimulation of low doses of cyclophosphamide.