In vivo cytokine gene therapy of human tumor xenografts in SCID mice by liposome-mediated DNA delivery.
The human interleukin-2 (IL-2) gene was successfully delivered into established human tumor xenografts in SCID (severe combined immunodeficient) mice by cationic liposome-mediated DNA delivery. A bicistronic mammalian expression vector containing a reporter gene (beta-galactosidase) and human IL-2 cDNA was complexed with either lipofectin or DC-cholesterol liposomes and transferred to tumor xenografts by direct intratumoral injection. Transfection of tumors was confirmed by staining of tumor sections for beta-galactosidase activity and by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of IL-2 mRNA. Growth suppression of tumor xenografts was observed in animals injected with plasmid-liposome complexes but not in animals that received liposomes or naked plasmid only. Complete tumor regression, mediated by the mouse natural killer cells, was observed in 50-80% of the mice treated with the plasmid containing the IL-2 cDNA. The effectiveness of the treatment was dependent on the transfection efficiency and the tumor size at the start of therapy. An initial IL-2 independent suppression of tumor growth was also observed with a plasmid carrying only the beta-galactosidase gene but this effect was temporary and did not lead to tumor regression. These results establish that human tumor xenografts growing in SCID mice can be transfected in vivo by liposome mediated gene delivery and that both IL-2-dependent and IL-2-independent factors may contribute to the tumor suppression observed here.
Egilmez
N K
NK
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cuenca
R
R
Yokota
S J
SJ
Sorgi
F
F
Bankert
R B
RB
D000818:Animals; D002455:Cell Division; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D003001:Cloning, Molecular; D004247:DNA; D015316:Genetic Therapy; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008081:Liposomes; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D008081:Liposomes; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D002784:Cholesterol