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Ixovex-1, a novel o...
Ixovex-1, a novel oncolytic E1B-mutated adenovirus
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- Anwar, Mohiemen (author)
- Chelsea & Westminster NHS Fdn Trust, ENT Dept, London, England.
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- Arendt, Maja-Louise (author)
- Univ Copenhagen, Dept Vet Clin Sci, Copenhagen, Denmark.
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- Ramachandran, Mohanraj, 1988- (author)
- Uppsala universitet,Cancerimmunterapi
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- Carlsson, Anette (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Essand, Magnus (author)
- Uppsala universitet,Cancerimmunterapi
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- Akusjärvi, Göran, 1953- (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Alusi, Ghasan (author)
- Ixogen Ltd, London, England.
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- Öberg, Daniel (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Chelsea & Westminster NHS Fdn Trust, ENT Dept, London, England Univ Copenhagen, Dept Vet Clin Sci, Copenhagen, Denmark. (creator_code:org_t)
- 2022-05-20
- 2022
- English.
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In: Cancer Gene Therapy. - : Springer Nature. - 0929-1903 .- 1476-5500. ; 29:11, s. 1628-1635
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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