胶质母细胞瘤
遗传增强
胶质瘤
干细胞
免疫疗法
脑瘤
靶向治疗
肿瘤科
放射治疗
从长凳到床边
病毒载体
作者
Chibawanye I. Ene,Juan Fueyo,Frederick F. Lang
出处
期刊:Neurosurgical Focus
[Journal of Neurosurgery Publishing Group]
日期:2021-02-01
卷期号:50 (2): 1-6
被引量:3
标识
DOI:10.3171/2020.11.focus20853
摘要
Delta-24-based oncolytic viruses are conditional replication adenoviruses developed to selectively infect and replicate in retinoblastoma 1 (Rb)-deficient cancer cells but not normal cell with intact Rb1 pathways. Over the years, there has been a significant evolution in the design of Delta-24 based on a better understanding of the underlying basis for infection, replication, and spread within cancer. One example is the development of Delta-24-RGD (DNX-2401), where the arginine-glycine-aspartate (RGD) domain enhances the infectivity of Delta-24 for cancer cells. DNX-2401 demonstrated objective biological and clinical responses during a phase I window of opportunity clinical trial for recurrent human glioblastoma. In long-term responders (> 3 years), there was evidence of immune infiltration (T cells and macrophages) into the tumor microenvironment with minimal toxicity. Although more in-depth analysis and phase III studies are pending, these results indicate that Delta-24-based adenovirus therapy may induce an antitumor response in glioblastoma, resulting in long-term antitumor immune response. In this review, the authors discuss the preclinical and clinical development of Delta-24 oncolytic adenoviral therapy for glioblastoma and describe structural improvements to Delta-24 that have enhanced its efficacy in vivo. They also highlight ongoing research that attempts to address the remaining obstacles limiting efficacy of Delta-24 adenovirus therapy for glioblastoma.
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