1. Ixovex-1, a novel oncolytic E1B-mutated adenovirus.
- Author
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Anwar M, Arendt ML, Ramachandran M, Carlsson A, Essand M, Akusjärvi G, Alusi G, and Öberg D
- Subjects
- Mice, Animals, Adenoviridae genetics, Adenoviridae metabolism, Adenovirus E1B Proteins genetics, Adenovirus E1B Proteins metabolism, Virus Replication genetics, Oncolytic Virotherapy methods, Oncolytic Viruses genetics, Oncolytic Viruses metabolism, Adenoviridae Infections, Neoplasms genetics, Neoplasms therapy
- Abstract
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., (© 2022. The Author(s).)
- Published
- 2022
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