Ixovex-1, a novel oncolytic E1B-mutated adenovirus

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  • Mohiemen Anwar
  • Arendt, Maja Louise
  • Mohanraj Ramachandran
  • Anette Carlsson
  • Magnus Essand
  • Göran Akusjärvi
  • Ghasan Alusi
  • Daniel Öberg

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.

Original languageEnglish
JournalCancer Gene Therapy
Volume29
Pages (from-to)1628–1635
ISSN0929-1903
DOIs
Publication statusPublished - 2022

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