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Production of an EGFR targeting molecule from a conditionally replicating adenovirus impairs its oncolytic potential

Cancer Gene Therapy volume 10, pages 583–588 (2003)Cite this article

Abstract

Oncolytic virotherapy with conditionally replicating viruses is a promising approach for treating advanced cancers. Promiscuous tropism and low tumor transduction have represented limiting issues, which targeting approaches seek to overcome. An approach utilizing a secretory targeting molecule for the epidermal growth factor pathway (sCAR-EGF) has previously been shown to be compatible with replicating adenoviruses, when an E1-deleted vector was used in a dual-virus system in conjunction with a replication-competent agent. Here, we constructed a virus that replicates in cancer cells and codes for sCAR-EGF. Interestingly, the oncolytic potency of the novel agent was not improved over nontargeted controls in vitro or in vivo. These results suggest that the expression of biologically active proteins can be counterproductive to virus replication.

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Acknowledgements

We thank Dr Bin Liu for help with virus production. This study was supported by the Sigrid Juselius Foundation, Emil Aaltonen Foundation, Maud Kuistila Foundation, Finnish Medical Foundation, Finnish Cancer Society, Biocentrum Helsinki, Lustgarten Foundation, Susan G Komen Foundation, the NCI (RO1 CA83821, P50 CA83591, P50 CA89019 R01 CA94084) and the University of Helsinki internal funds.

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Authors and Affiliations

  1. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, University of Alabama at Birmingham, 35294-3300, Alabama, USA

    Akseli Hemminki, Minghui Wang & David T Curiel

  2. The Gene Therapy Center, University of Alabama at Birmingham, 35294-3300, Alabama, USA

    Akseli Hemminki, Minghui Wang & David T Curiel

  3. Department of Oncology, Rational Drug Design Program, Biomedicum, 00014, University of Helsinki, Finland

    Akseli Hemminki

  4. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland

    Tanja Hakkarainen & Jarmo Wahlfors

  5. Comprehensive Cancer Center Biostatistics Unit, University of Alabama at Birmingham, 35294-2172, Alabama, USA

    Renee A Desmond

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  1. Akseli Hemminki
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Correspondence to Akseli Hemminki.

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Hemminki, A., Wang, M., Hakkarainen, T. et al. Production of an EGFR targeting molecule from a conditionally replicating adenovirus impairs its oncolytic potential. Cancer Gene Ther 10, 583–588 (2003). https://doi.org/10.1038/sj.cgt.7700606

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  • DOI: https://doi.org/10.1038/sj.cgt.7700606

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