MONOCYTE ACTIVATION FOLLOWING SYSTEMIC ADMINISTRATION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Twenty-four patients with solid malignancies were treated with granulo cyte-macrophage colony-stimulating factor (GM-CSF) on a Phase 1b trial . The objective of the study was to evaluate the effects of GM-CSF on peripheral blood monocyte activation. GM-CSF was administered by subcu taneous injection daily for 14 days. Immune parameters measured were m onocyte cytotoxicity against the human colon carcinoma (HT29) cell lin e, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, a nd in vitro TNF-alpha. and IL-1 beta induction. All patients were eval uable for toxicity. Fifteen patients were evaluable for immunologic re sponse. Treatment with GM-CSF led to a statistically significant enhan cement in direct monocyte cytotoxicity against HT29 cells. There was n o increase in serum TNF-alpha or IL-1 beta and no consistent in vitro induction of TNF-alpha. or IL-1 beta from monocytes posttreatment. Tre atment was well tolerated overall. We conclude that treatment with GM- CSF can lead to enhanced monocyte cytotoxicity. Further studies are in progress to evaluate the effect of GM-CSF on other parameters of mono cyte functions.