Ixovex-1, a novel oncolytic E1B-mutated adenovirus

Anwar, MohiemenChelsea & Westminster NHS Fdn Trust, ENT Dept, London, England. (author)

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.

Arendt, Maja-LouiseUniv Copenhagen, Dept Vet Clin Sci, Copenhagen, Denmark. (author)
Ramachandran, Mohanraj,1988-Uppsala universitet,Cancerimmunterapi(Swepub:uu)mohra272 (author)
Carlsson, AnetteUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)aca31040 (author)
Essand, MagnusUppsala universitet,Cancerimmunterapi(Swepub:uu)magnessa (author)
Akusjärvi, Göran,1953-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)gak30132 (author)
Alusi, GhasanIxogen Ltd, London, England. (author)
Öberg, DanielUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)daobe475 (author)
Chelsea & Westminster NHS Fdn Trust, ENT Dept, London, England.Univ Copenhagen, Dept Vet Clin Sci, Copenhagen, Denmark. (creator_code:org_t)

By the author/editor: Anwar, Mohiemen; Arendt, Maja-Lou ...; Ramachandran, Mo ...; Carlsson, Anette; Essand, Magnus; Akusjärvi, Göran ...; show more...; Alusi, Ghasan; Öberg, Daniel; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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