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[Use of gene therapy in a subcutaneous murine model of lung cancer]
Manuel Rodrigo Garzón1, Iñigo Tirapu Fernández de la Cuesta, Ainhoa Arina Iraeta
1Servicio de Neumología, Clínica Universitaria de Navarra, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, España. manrrogar@yahoo.es
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.
Insights
Gene therapy using AdCMV-Tk, AdCMV-IL12, or DC-IL12 effectively reduced subcutaneous Lewis lung cancer tumor growth in mice. This in vivo gene therapy demonstrated significant and sustained tumor reduction compared to control groups.
Area of Science:
- Oncology
- Gene Therapy
- Immunotherapy
Context:
- Subcutaneous tumors were generated from murine Lewis lung cancer cells in C57BL/6 mice.
- Tumor growth was monitored for 3-4 weeks post-treatment.
- Gene therapy vectors included replication-defective adenovirus carrying thymidine kinase (AdCMV-Tk) or interleukin-12 (AdCMV-IL12), and dendritic cells transduced with IL-12 (DC-IL12).
Purpose:
- To evaluate the efficacy of in vivo gene therapy in treating established subcutaneous lung cancer tumors.
- To compare the therapeutic effects of AdCMV-Tk, AdCMV-IL12, and DC-IL12 against control treatments.
Summary:
- All tested gene therapy modalities (AdCMV-Tk, AdCMV-IL12, DC-IL12) resulted in a statistically significant reduction in tumor growth.
- The reduction in tumor size was significant from day 7-10 and maintained throughout the study period.
- Control groups received saline or AdCMV-LacZ (reporter gene) and showed no therapeutic effect.
Impact:
- Demonstrates the potential of in vivo gene therapy as a viable treatment strategy for lung cancer.
- Highlights AdCMV-Tk, AdCMV-IL12, and DC-IL12 as promising agents for reducing tumor burden.
- Provides a preclinical basis for further investigation of these gene therapy approaches in lung cancer treatment.
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