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Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells
P Haghighat1, T M Timiryasova, B Chen
1Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, CA 92350, USA.
Abstract:
The use of interleukin-2 (IL-2) and p53 for immunotherapy and gene therapy for cancer has shown promising results. In this study, we examined the efficacy of plasmid gene therapy utilizing murine IL-2, the wild-type (wt) human p53 gene, the combination of these genes, and the murine bax gene, which are under the control of the cytomegalovirus (CMV) immediate-early promoter, in nude mice bearing established subcutaneous C6 glioma. In vitro assays and immunocytochemical analysis for therapeutic genes demonstrated expression of the proteins in C6 transfected cells. In animal studies, significant antitumor activity was observed for the IL-2, p53/IL-2, and bax treated groups. However, no synergistic effect was observed in the p53/IL-2 combination group. Demonstrating for the first time, bax showed a significant reduction of tumor volume when compared to p53 (p < 0.02). Thus, our in vivo studies show that delivery of naked therapeutic genes is safe and results in significantly slower progression of glioma in athymic rodents.
Insights
This study explored gene therapy for glioma using interleukin-2 (IL-2), p53, and bax genes. Bax gene therapy significantly reduced tumor volume in mice, showing promise for glioma treatment.
Area of Science:
- Oncology
- Gene Therapy
- Immunotherapy
Background:
- Interleukin-2 (IL-2) and p53 are investigated for cancer immunotherapy and gene therapy.
- Previous research indicates potential benefits of IL-2 and p53 in cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of plasmid gene therapy using murine IL-2, wild-type human p53, and murine bax genes in C6 glioma-bearing nude mice.
- To assess the antitumor activity and safety of individual and combined gene therapies.
Main Methods:
- In vitro assays and immunocytochemical analysis confirmed protein expression in transfected C6 cells.
- Nude mice with established subcutaneous C6 glioma were treated with naked plasmid DNA encoding IL-2, p53, bax, or combinations thereof.
- Tumor volume and progression were monitored in vivo.
Main Results:
- Significant antitumor activity was observed in groups treated with IL-2, p53/IL-2, and bax.
- The bax gene demonstrated a significant reduction in tumor volume compared to p53 (p < 0.02).
- No synergistic effect was found for the p53/IL-2 combination therapy.
Conclusions:
- Naked gene delivery of IL-2, p53, and bax is safe for glioma treatment in vivo.
- Bax gene therapy shows significant efficacy in reducing glioma tumor volume.
- Gene therapy holds promise for slowing glioma progression in athymic rodents.
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