[Use of gene therapy in a subcutaneous murine model of lung cancer]. / Aplicación de tratamiento génico a un modelo subcutáneo de cáncer de pulmón murino.

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 x 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 beta-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 AdCMV-Tk, 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, AdCMV-IL12, 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.

Aplicación de tratamiento génico a un modelo subcutáneo de cáncer de pulmón murino / Use of gene therapy in a subcutaneous murine model of lung cancer

Objetivo: Demostrar la utilidad del tratamiento génico (TG) in vivo en los tumores subcutáneos de cáncer de pulmón murino. Material y métodos: Se inyectaron a ratones C57BL/6 por vía subcutánea 5 x 105 células de la línea de cáncer de pulmón murino de Lewis. A los 10 días se formaron tumores subcutáneos de unos 5 mm de diámetro. En ese momento se trataron mediante inyección intratumoral con un adenovirus recombinante defectivo portador del gen de la timidincinasa (AdCMV-Tk), o del gen de la interleucina 12 (AdCMV-IL12), o con células dendríticas (CD) singénicas transducidas con el gen de la interleucina 12 (CD-IL12). Como grupos control se incluyeron tumores tratados con suero salino o con un adenovirus con el gen de la β-galactosidasa (AdCMV-LacZ), que es un gen indicador sin efecto terapéutico. El número de animales por grupo osciló entre 14 y 25 con adenovirus y entre 10 y 12 con CD. A continuación se realizó un seguimiento del tamaño tumoral desde el primer día de tratamiento hasta la tercera (adenovirus) o cuarta (CD) semanas para comparar su evolución. Resultados: Se objetivó una disminución significativa del crecimiento de los tumores subcutáneos en los grupos tratados con AdCMV-Tk, AdCMV-IL12 y CD-IL12 comparados con los grupos control tratados con suelo salino y AdCMV-LacZ. En el grupo AdCMV-Tk esta diferencia fue estadísticamente significativa desde el día 7, en AdCMV-IL12 desde el día 9 y en CD-IL12 desde el día 10 y se mantuvo hasta el final del seguimiento. Conclusiones: El TG con AdCMV-Tk, AdCMV-IL12 o CD-IL12 es efectivo en nuestro modelo de tumores subcutáneos de células de carcinoma pulmonar de Lewis, ya que es capaz de disminuir su tasa de crecimiento de forma significativa respecto a los grupos de control

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 x 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 AdCMV-Tk, 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, AdCMV-IL12, 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