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Ixovex-1, a novel oncolytic E1B-mutated adenovirus.
Anwar, Mohiemen; Arendt, Maja-Louise; Ramachandran, Mohanraj; Carlsson, Anette; Essand, Magnus; Akusjärvi, Göran; Alusi, Ghasan; Öberg, Daniel.
Afiliación
  • Anwar M; ENT department, Chelsea and Westminster NHS Foundation Trust, London, UK.
  • Arendt ML; Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Ramachandran M; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Carlsson A; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala Biomedical Centre, Uppsala, Sweden.
  • Essand M; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
  • Akusjärvi G; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala Biomedical Centre, Uppsala, Sweden.
  • Alusi G; Ixogen Ltd, London, UK.
  • Öberg D; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala Biomedical Centre, Uppsala, Sweden. Danieloberg1000@gmail.com.
Cancer Gene Ther ; 29(11): 1628-1635, 2022 11.
Article en En | MEDLINE | ID: mdl-35596069
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Adenoviridae / Virus Oncolíticos / Viroterapia Oncolítica / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Adenoviridae / Virus Oncolíticos / Viroterapia Oncolítica / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido