Combined therapy of B16(F10) murine melanoma using E-coli cytosine deaminase gene and murine interleukin-4 gene

This paper summarizes preliminary results of combining suicide gene strateg y (E.coli cytosine deaminase gene - CD) with immunotherapy (murine interleu kin-4 gene) for treatment of experimental B16(F10) melanomas implanted into C57B1/ 6 mice. The best therapeutic results, inhibition of tumor growth an d prolonged survival time of treated vs. control mice, were obtained when p lasmid expression vectors containing therapeutic genes were transferred int o mice via DDAB/DOPE cationic liposome carrier on the third or fourth day f ollowing inoculation of mice with cancer cells. Extension of survival time has been noted in the case of two-gene therapy (as compared with one-gene t herapy) of tumors which originated from cells transfected in vitro with CD gene and which were subsequently injected in vivo with IL-4-secreting cells . However, no improvement of therapeutic effect was obtained in case of mic e treated with a combination of two genes transferred intratumorally with D DAB/DOPE cationic liposomes as compared to mice treated with a single gene only.