SummaryThe purpose of these studies was to determine whether recombinant tumor necrosis factor (TNF) incorporated into liposomes produced enhanced antitumor effects against TNF-sensitive and TNF-resistant target cells. The lipid composition of liposomes influenced their binding to and endocytosis by target cells. Liposomes consisting of phosphatidylcholine and phosphatidylserine (7:3 molar ratio) bound to L929 cells and A375 human melanoma cells, albeit to different degrees. Liposomes retained encapsulated TNF for up to 48 h of incubation. TNF in liposomes lysed the TNF-sensitive A375 melanoma and L929 cells at levels similar to that mediated by free, unencapsulated TNF. Cells selected for resistance against free TNF were not sensitive to TNF in liposomes. Since liposomes concentrate in organs with high levels of reticuloendothelial activity, and TNF in liposomes retains antitumor activity, this delivery system may prove to be useful for treatment of lymph node and hepatic metastases