In vivo transfer of bacterial marker genes results in differing levels of gene expression and tumor progression in immunocompetent and immunodeficient mice

To optimize gene delivery for the treatment of malignant mesothelioma, expr ession of the beta-galactosidase marker gene was examined in a murine model of intraperitoneal malignant mesothelioma. The beta-galactosidase gene was delivered to the peritoneal cavity of tumor-bearing mice by various plasmi d-liposome complexes or by replication-incompetent retrovirus, used alone o r complexed to liposomes. In tumor samples from immunodeficient nude mice, moderate levels of gene expression were achieved by liposome-complexed plas mids. Retroviral gene delivery was more effective, and was increased nearly 10-fold by complexing the retrovirus to liposomes. In contrast, in tumor s amples from immunocompetent CBA mice treated,vith the same vectors, no mark er gene expression was detected. In immunodeficient mice, tumor growth was not affected by beta-galactosidase gene transfer. However, immunocompetent mice showed a significant decrease in tumor size and increase in survival t ime after beta-galactosidase delivery. Induction of cytotoxic T cells capab le of lysing beta-Gal-transfected tumor cells suggests that tumor cells tra nsduced with the bacterial beta-galactosidase gene may be eliminated in imm unocompetent hosts. Our findings also indicate that plasmid-liposome comple xes, which achieve a low level of gene expression, and retrovirus-liposome complexes, which result in nearly 100 times higher levels of gene expressio n in tumor cells in vivo, are similarly effective in inducing an antitumor immune response.