Use of Gene Therapy in a Subcutaneous Murine Model of Lung Cancer
Aplicación de tratamiento oncogénico a un modelo subcutáneo de cáncer de pulmón murino
Rodrigo Garzon M, Tirapu Fernandez de la Cuesta,I., Arina Iraeta A, Centelles Llorente MN, Zulueta Frances J. Use of gene therapy in a subcutaneous murine model of lung cancer. Arch Bronconeumol 2006 Oct;42(10):526-532
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.
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