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白细胞介素 2 和 rAd-p53 治疗脑胶质母细胞瘤的疗效。

The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma.

机构信息

Department of Neurosurgery, Tianjin Nankai Hospital, Tianjin 300100, P.R. China.

出版信息

Mol Med Rep. 2018 Mar;17(3):4853-4859. doi: 10.3892/mmr.2018.8408. Epub 2018 Jan 9.

Abstract

Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model. In addition, the activity of IL‑2 was analyzed. The antitumor potential of IL‑2 and rAd‑p53 was studied using xenograph mice carrying GBM cells. Tumor‑specific CD4+ and CD8+ T cells were also analyzed in the GBM‑bearing models. The results demonstrated that IL‑2 and rAd‑p53 not only stimulated tumor‑specific cytotoxic T‑lymphocyte responses and increased regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally increased expression of apoptosis‑associated genes. The treatment with IL‑2 and rAd‑p53 resulted in tumor regression and prolonged the survival of glioma‑bearing mice. Taken together, a combination of IL‑2 and rAd‑p53 treatment combines the effects of immunotherapy and oncolytic therapy and may be a comprehensive therapeutic schedule for clinical application in future cancer therapies.

摘要

白细胞介素 2(IL-2)是一种抗癌细胞因子,可刺激 T 细胞增殖,触发先天和适应性免疫。IL-2 已被用于癌症治疗,并取得了疗效。重组腺病毒 p53 注射(rAd-p53)是一种基因治疗药物,可能改善胶质母细胞瘤(GBM)患者的预后。本研究研究了 IL-2 和 rAd-p53 联合治疗的效果。在 GBM 肿瘤模型中研究了 IL-2 刺激免疫调节的能力和 p53 诱导 GBM 细胞凋亡的能力。此外,还分析了 IL-2 的活性。使用携带 GBM 细胞的异种移植小鼠研究了 IL-2 和 rAd-p53 的抗肿瘤潜力。还在 GBM 荷瘤模型中分析了肿瘤特异性 CD4+和 CD8+T 细胞。结果表明,IL-2 和 rAd-p53 不仅刺激了肿瘤特异性细胞毒性 T 淋巴细胞反应,增加了调节性 CD4+和细胞毒性 CD8+T 细胞的增殖,而且还增加了凋亡相关基因的表达。IL-2 和 rAd-p53 的联合治疗导致肿瘤消退,并延长了荷瘤小鼠的生存时间。总之,IL-2 和 rAd-p53 的联合治疗结合了免疫治疗和溶瘤治疗的效果,可能是未来癌症治疗中临床应用的综合治疗方案。

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