Suzuki K, Fueyo J, Krasnykh V, Reynolds P N, Curiel D T, Alemany R
Gene Therapy Center, University of Alabama at Birmingham, 35294-3300, USA.
Clin Cancer Res. 2001 Jan;7(1):120-6.
The absence or the presence of low levels of the Coxsackievirus and adenovirus receptor (CAR) on several tumor types might limit the efficacy of recently proposed tumor-specific or conditionally replicative adenoviruses (CRAds). To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target cell infection as a means to enhance oncolytic potency. Such infectivity-enhanced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber-modified CRAd could be demonstrated in vivo. We conclude that the combination of genomic modification to achieve tumor-selective replication and capsid modification to enhance infectivity yields more potent oncolytic adenoviruses for use in cancer treatment.
几种肿瘤类型中柯萨奇病毒和腺病毒受体（CAR）的缺失或低水平表达可能会限制最近提出的肿瘤特异性或条件性复制腺病毒（CRAds）的疗效。为了解决这个问题，我们在E1A缺陷型CRAd的背景下对纤维结进行了基因改造，以实现不依赖CAR的靶细胞感染，作为增强溶瘤效力的一种手段。这种感染性增强的CRAd在体外显示出更高的复制能力、更有效的感染能力以及对肿瘤细胞的裂解能力。值得注意的是，纤维修饰的CRAd在体内也能表现出改善的抗肿瘤效果。我们得出结论，基因组修饰以实现肿瘤选择性复制与衣壳修饰以增强感染性相结合，可产生更有效的溶瘤腺病毒用于癌症治疗。
