Haghighat P, Timiryasova T M, Chen B, Kajioka E H, Gridley D S, Fodor I
Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, CA 92350, USA.
Anticancer Res. 2000 May-Jun;20(3A):1337-42.
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.
白细胞介素-2（IL-2）和p53用于癌症免疫治疗和基因治疗已显示出有前景的结果。在本研究中，我们检测了利用鼠IL-2、野生型（wt）人p53基因、这些基因的组合以及鼠bax基因的质粒基因治疗的疗效，这些基因受巨细胞病毒（CMV）立即早期启动子控制，用于接种了皮下C6胶质瘤的裸鼠。对治疗性基因的体外测定和免疫细胞化学分析证明了蛋白质在C6转染细胞中的表达。在动物研究中，IL-2、p53/IL-2和bax治疗组观察到显著的抗肿瘤活性。然而，p53/IL-2组合组未观察到协同效应。首次证明，与p53相比，bax显示肿瘤体积显著减小（p < 0.02）。因此，我们的体内研究表明，裸治疗性基因的递送是安全的，并且在无胸腺啮齿动物中导致胶质瘤进展显著减慢。
