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 es tablished human tumor xenografts in SCID (severe combined immunodefici ent) mice by cationic liposome-mediated DNA delivery. A bicistronic ma mmalian expression vector containing a reporter gene (beta-galactosida se) and human IL-2 cDNA was complexed with either lipofectin or DC-cho lesterol liposomes and transferred to tumor xenografts by direct intra tumoral injection. Transfection of tumors was confirmed by staining of tumor sections for beta-galactosidase activity and by reverse transcr iption-polymerase chain reaction (RT-PCR) for the presence of IL-2 mRN A. Growth suppression of tumor xenografts was observed in animals inje cted with plasmid-liposome complexes but not in animals that received liposomes or naked plasmid only. Complete tumor regression, mediated b y the mouse natural killer cells, was observed in 50-80% of the mice t reated with the plasmid containing the IL-2 cDNA. The effectiveness of the treatment was dependent on the transfection efficiency and the tu mor size at the start of therapy. An initial IL-2 independent suppress ion of tumor growth was also observed with a plasmid carrying only the beta-galactosidase gene but this effect was temporary and did not lea d to tumor regression. These results establish that human tumor xenogr afts growing in SCID mice can be transfected in vivo by liposome media ted gene delivery and that both IL-2-dependent and IL-2-independent fa ctors may contribute to the tumor suppression observed here.