论文标题：The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

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作者：Naiara Martínez-Vélez, Marc Garcia-Moure, Miguel Marigil, Marisol González-Huarriz, Montse Puigdelloses, Jaime Gallego Pérez-Larraya, Marta Zalacaín, Lucía Marrodán, Maider Varela-Guruceaga, Virginia Laspidea, Jose Javier Aristu, Luis Isaac Ramos, Sonia Tejada-Solís, Ricardo Díez-Valle, Chris Jones, Alan Mackay, Jose A. Martínez-Climent, Maria Jose García-Barchino, Eric Raabe, Michelle Monje, Oren J. Becher, Marie Pierre Junier, Elias A. El-Habr, Herve Chneiweiss, Guillermo Aldave, Hong Jiang, Juan Fueyo, Ana Patiño-García, Candelaria Gomez-Manzano, Marta M. Alonso,

发表时间：2019/05/28

数字识别码： 10.1038/s41467-019-10043-0

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根据《自然-通讯》发表的一项研究The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models，一种溶瘤病毒（靶向癌细胞的病毒）有效延长了两种不同类型儿童脑肿瘤模型小鼠的存活时间。这些发现促使研究人员利用该病毒展开了一项长期临床试验。

图1：Delta-24-RGD病毒在pHGG 和 DIPG模型中的复制和感染

图源：Naiara Martínez-Vélez

儿童脑肿瘤如高级别胶质瘤和弥漫内生性脑桥胶质瘤难以治疗，而且与成人肿瘤相比具有遗传差异性。高级别胶质瘤患者的治疗方法是手术、放疗和化疗；但是手术不适合患有弥漫内生性脑桥胶质瘤的儿童患者。美国FDA已经批准将溶瘤病毒用于治疗黑素瘤，而且现已表明Delta-24-RGD病毒对胶质瘤成年患者不仅有效也安全。

西班牙纳瓦拉健康研究所的Marta Alonso及同事利用高级别胶质瘤和弥漫内生性脑桥胶质瘤模型小鼠，检验Delta-24-RGD病毒的有效性。他们发现与未经治疗的小鼠相比，在四种不同的癌症模型中，实验小鼠的存活时间延长了。而且在长期存活的小鼠中未检测到病毒蛋白，这意味着这种方法是安全的。进一步的研究表明，病毒在小鼠体内触发了免疫响应，这意味着免疫系统的激活促成了抗癌响应。以上发现表明，这种方法或能用于治疗患有此类肿瘤的儿童患者，但是这一点还需要试验验证。

摘要：Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).

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