文章：

Ixovex-1，一种新的溶瘤性e1b突变腺病毒

Ixovex-1, a novel oncolytic E1B-mutated adenovirus 

原文发布日期：2022-05-20 

英文摘要：

There is a great demand for improved oncolytic viruses that selectively replicate within cancer cells while sparing normal cells. Here, we describe a novel oncolytic adenovirus, Ixovex-1, that obtains a cancer-selective replication phenotype by modulating the level of expression of the different, alternatively spliced E1B mRNA isoforms. Ixovex-1 is a recombinant adenovirus that carries a single point mutation in the E1B-93R 3’ splice acceptor site that results in overexpression of the E1B-156R splice isoform. In this paper, we studied the characteristics of this novel oncolytic adenovirus by validating its in vitro behaviour in a panel of normal cells and cancer cells. We additionally studied its anti-tumour efficacy in vivo. Ixovex-1 significantly inhibited tumour growth and prolonged survival of mice in an immune-deficient lung carcinoma tumour implantation model. In complementation experiments, overexpression of E1B-156R was shown to increase the oncolytic index of both Ad5wt and ONYX-015. In contrast to prior viruses of similar type, Ixovex-1 includes a functional E3B region for better in vivo efficacy. Throughout this study, the Ixovex-1 virus has been proven to be superior in competency compared to a virus with multiple deletions. 

摘要翻译： 

目前对改良型溶瘤病毒的需求巨大，这类病毒能选择性地在癌细胞内部复制而不损伤正常细胞。本研究开发了一种新型溶瘤腺病毒Ixovex-1，其通过调控不同选择性剪接的E1B mRNA亚型的表达水平实现癌症选择性复制表型。该重组腺病毒在E1B-93R的3'剪接受体位点携带单点突变，导致E1B-156R剪接亚型过表达。我们通过在多组正常细胞和癌细胞中验证其体外行为，研究了该新型溶瘤病毒的特性，并进一步评估了其体内抗肿瘤功效。在免疫缺陷型肺癌移植瘤模型中，Ixovex-1显著抑制肿瘤生长并延长小鼠生存期。互补实验表明，E1B-156R过表达能增强Ad5wt和ONYX-015的溶瘤指数。与既往同类病毒相比，Ixovex-1保留了功能性E3B区域以提升体内疗效。本研究证实，Ixovex-1病毒在效能上显著优于多重缺失型病毒。

原文链接：

Ixovex-1, a novel oncolytic E1B-mutated adenovirus