OBJECTIVE: To assess the effectiveness of in vivo gene
therapy to treat subcutaneous tumors generated from murine
lung cancer cells.
MATERIAL AND METHODS: C57BL/6 mice received
subcutaneus injections of 5×105 cells from the murine Lewis
lung cancer cell line. By 10 days, subcutaneous tumors of
approximately 5 mm diameter were formed. At that point,
treatment was provided by intratumor injection of a
replication-defective recombinant adenovirus carrying the
gene for thymidine kinase (AdCMV-Tk) or interleukin (IL)
12 (AdCMV-IL12), or by injection of syngeneic dendritic
cells previously transduced with adenovirus containing the
IL-12 gene (DC-IL12). Control groups were treated with
saline or adenovirus containing the gene for β-galactosidase
(AdCMV-LacZ), which functions as a reporter gene and
does not have a therapeutic effect. The number of animals in
each group ranged from 14 to 25 in experiments using
adenovirus and from 10 to 12 in experiments using dendritic
cells. Tumor size was followed for 3 weeks in the case of
treatment with adenovirus and 4 weeks for treatment with
dendritic cells.
RESULTS: A significant reduction in subcutaneous tumor
growth was observed in the groups treated with AdCMVTk,
AdCMV-IL12, and DC-IL12 compared with control
groups treated with saline or AdCMV-LacZ. The difference
was statistically significant from day 7 of treatment in the
AdCMV-Tk group, from day 9 in the AdCMV-IL12 group,
and from day 10 in the DC-IL12 group, and in all cases it
was maintained until the end of the follow-up period.
CONCLUSIONS: Gene therapy with AdCMV-Tk, AdCMVIL12,
or DC-IL12 is effective in our model of subcutaneous
tumors arising from cells of the Lewis lung cancer cell line.
The treatment leads to a significant reduction in tumor
growth compared with control groups
