Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35294-6832, USA.
Cancer Gene Ther. 2009 Oct;16(10):794-805. doi: 10.1038/cgt.2009.23. Epub 2009 Apr 10.
Malignant forms of glioma, the most common primary brain tumors, remain poorly responsive to multimodality therapeutic interventions, including chemotherapy. Suppressed apoptosis and extraordinary invasiveness are important distinctive features that contribute to the malignant phenotype of glioma. We have developed the vascular endothelial growth factor receptor 1 (VEGFR-1/flt-1) conditional replicating adenoviral vector (CRAdRGDflt-IL24) encoding the interleukin-24 (IL-24) gene. We investigated whether a combination of CRAdRGDflt-IL24-mediated oncolytic virotherapy and chemotherapy using temozolomide (TMZ) produces increased cytotoxicity against human glioma cells in comparison with these agents alone. Combination of CRAdRGDflt-IL24 and TMZ significantly enhanced cytotoxicity in vitro, inhibited D54MG tumor growth and prolonged survival of mice harboring intracranial human glioma xenografts in comparison with CRAdRGDflt-IL24 or TMZ alone. These data indicate that combined treatment with CRAdRGDflt-IL24-mediated oncolytic virotherapy and TMZ chemotherapy provides a promising approach for glioma therapy.
恶性脑胶质瘤是最常见的原发性脑肿瘤,对包括化疗在内的多种治疗方法反应不佳。凋亡受抑和极强的侵袭性是导致胶质瘤恶性表型的重要特征。我们已经开发了血管内皮生长因子受体 1(VEGFR-1/flt-1)条件复制型腺病毒载体(CRAdRGDflt-IL24),可编码白细胞介素 24(IL-24)基因。我们研究了与单独使用这些药物相比,CRAdRGDflt-IL24 介导的溶瘤病毒治疗联合替莫唑胺(TMZ)化疗是否会增加对人胶质瘤细胞的细胞毒性。与单独使用 CRAdRGDflt-IL24 或 TMZ 相比,CRAdRGDflt-IL24 和 TMZ 的联合治疗显著增强了体外细胞毒性,抑制了 D54MG 肿瘤的生长,并延长了携带颅内人胶质细胞瘤异种移植物的小鼠的存活时间。这些数据表明,CRAdRGDflt-IL24 介导的溶瘤病毒治疗联合 TMZ 化疗的联合治疗为胶质瘤治疗提供了一种很有前途的方法。