In vivo antitumor effect of cationic liposomes containing diphtheria toxin A-chain gene on cells infected with bovine leukemia virus.

A plasmid pLTR-DT which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (BLV-LTR) in the multicloning site of pUC-18 was entrapped in cationic liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG), dioleoyl phosphatidylethanolamine (DOPE) and dilauroyl phosphatidylcholine (DLPC) (1:2:2, molar ratio) (TMAG-liposome), and their antitumor effect on BLV-infected tumor cells was examined in vivo. The cationic TMAG-liposome containing pLTR-DT was successively injected into the tumor transplanted to nude mice. The growth of tumor was significantly inhibited by the injection of cationic TMAG-liposome containing pLTR-DT. On the other hand, TMAG-liposome containing pUC18 plasmids showed no such effect. These results suggest that a DT-A expression plasmid under the control of BLV-LTR is highly toxic to the BLV-infected tumor cells, and that the cationic liposomes, such as TMAG-liposome, may be efficient transfection reagent for BLV-infected tumor cells and can be utilized for DT-A gene delivery into BLV-infected tumor cells in vivo.