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  • The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors.

The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors.

Gene therapy (1996-11-01)
S Szala, E Missol, A Sochanik, M Strozyk
ABSTRACT

An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cytosine deaminase 'suicide' gene under the control of tissue-specific tyrosinase gene promoter directly into the murine melanoma B16(F10) tumor. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine melanoma B16(F10) tumor growth and, in some cases, rejection of the pre-established tumor. The inhibition of tumor growth expressed as the increased survival of mice is better seen in the case of using DNA-DDAB/DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5-fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), increased transfection efficiency of surviving cancer cells (in this case DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cholesteryl 3β-N-(di­methyl­amino­ethyl)­carbamate hydrochloride, ≥95%
Sigma-Aldrich
L-α-Phosphatidylethanolamine, dioleoyl, ≥99% (GC), ≥98% (TLC), lyophilized powder