A combined gene delivery by co-transduction of adenoviral and retroviral vectors for cancer gene therapy

A novel second generation retroviral producer cell strategy (an adenoviral/retroviral combined delivery system) has been developed by this laboratory. In the present studies, this delivery system was used to examine its delivery efficiency in vitro and in vivo by using a marker gene, LacZ, and a therapeutic gene, herpes simplex virus thymidine kinase (HSV-tk), both of which were transduced into a tumor cell line KBALB. In the in vitro experiments for delivery efficacy of the LacZ gene, the delivery efficiency of KBALB+KBALBLNPOZAdN/H (1:1) was 27.8% higher than that of KBALB+KBALBLNPOZ (1:1) (P<0.01). For the antitumor effect of HSV-tk/ganciclovir (GCV), the death ratio of KBALB+KBALBLNCTKAdN/H (1:1) was higher than that of KBALB+KBALBLNCTK (1:1), on 4, 6, and 8 days at a concentration of 0.1, 1, and 10 μg/ml, respectively (P<0.01 or P<0.05). In the in vivo experiments for LacZ gene expression, the delivery efficiency in KBALB+KBALBLNPOZAdN/H (1:1) was 21.5% more efficient than that in KBALB+KBALBLNPOZ (1:1) (P<0.01). For HSV-tk/GCV antitumor effect, the suppression of tumors by KBALB+KBALBLNCTKAdN/H (1:1) was more effective than that by KBALB+KBALBLNCTK (1:1) (P<0.05). Results suggest that this new delivery system is more efficient than the traditional in vitro and in vivo retroviral vector delivery system.