Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Texas, USA.
Curr Gene Ther. 2009 Oct;9(5):422-7. doi: 10.2174/156652309789753356.
Oncolytic adenoviruses are emerging as a promising alternative therapy for glioma patients and are currently being tested in clinic. In this review, we summarize our experience with gene-based therapy targeting RB pathway in gliomas. Our study has evolved from the development of RB-expressing adenoviral vectors to the characterization of the oncolytic effects on gliomas of the replication competent adenoviruses Delta-24, Delta-24-RGD and ICOVIR. We also review the successful combination of the viruses with chemotherapies that are routinely used in glioma patients, the efficacy of Delta-24-RGD against brain tumor stem cells, the newly described adenovirus-induced autophagy and the potential for the systemic delivery of the oncolytic viruses with human mesenchymal stem cells. Finally, we comment on the preclinical and clinical studies of p53 expressing adenoviral vector and the lessons learned from the experience of Onyx-015, the first oncolytic adenovirus tested in clinical setting.
溶瘤腺病毒作为一种治疗脑胶质瘤的有前途的替代疗法，目前正在临床试验中进行测试。在这篇综述中，我们总结了我们在针对 RB 通路的基因治疗方面的经验，这些经验是针对脑胶质瘤的。我们的研究从表达 RB 的腺病毒载体的开发，发展到对复制型腺病毒 Delta-24、Delta-24-RGD 和 ICOVIR 对脑胶质瘤的溶瘤作用的特征描述。我们还回顾了病毒与常规用于脑胶质瘤患者的化疗药物联合应用的成功，Delta-24-RGD 对脑肿瘤干细胞的疗效，新描述的腺病毒诱导的自噬，以及利用人骨髓间充质干细胞进行全身递送溶瘤病毒的潜力。最后，我们对表达 p53 的腺病毒载体的临床前和临床研究进行了评论，并从在临床环境中进行测试的第一个溶瘤腺病毒 Onyx-015 的经验中吸取了教训。
