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  • Original Article
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Augmented adenovirus transduction of murine T lymphocytes utilizing a bi-specific protein targeting murine interleukin 2 receptor

A Corrigendum to this article was published on 23 April 2015

Abstract

Adenoviruses are currently used in a variety of bench and bedside applications. However, their employment in gene delivery to lymphocyte lineages is hampered by the lack of coxsackie virus and adenovirus receptor (CAR) on the cell surface. Exploitation of an alternative receptor on the surface of T lymphocytes can allow for utilization of adenovirus in a variety of T lymphocyte-based diseases and therapies. Here, we describe how resistance to infection can be overcome by the utilization of a bi-specific fusion protein, soluble CAR murine interleukin 2 (sCAR-mIL-2), that retargets adenovirus to the murine IL-2 receptor (IL-2R). Infection of a murine T-cell line, CTLL-2, with a sCAR-mIL-2/Adenovirus conjugate provided a ninefold increase in both green fluorescence protein-positive cells and luciferase expression. In addition, this increase in infection was also seen in isolated primary murine T lymphocytes. In this context, the sCAR-mIL-2 adapter provided a fourfold gene transduction increase in activated primary murine T lymphocytes. Our results show that recombinant sCAR-mIL-2 fusion protein promotes IL-2R-targeted gene transfer to murine T lymphocytes and that alternative targeting can abrogate their native resistance to infection.

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Acknowledgements

I would like to thank Dr Alexander Pereboev. He was instrumental in the planning and early stages of developing the sCAR-mIL-2. He passed away before this work was completed; he will be greatly missed. The adenovirus shuttle plasmid, pSH-UP-UP-GFP (R) was kindly provided by Dr J. DeGregori (University of Colorado School of Medicine, Denver, CO, USA). The plasmids for the self-inactivating lentiviral vector were kindly provided by Dr Justin Roth (University of Alabama at Birmingham, Birmingham, AL, USA). The rabbit polyclonal anti-CAR antibody was a kind gift of Dr Hideyo Ugai (Washington University in St Louis, St Louis, MO, USA).

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Correspondence to D T Curiel.

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Beatty, M., Curiel, D. Augmented adenovirus transduction of murine T lymphocytes utilizing a bi-specific protein targeting murine interleukin 2 receptor. Cancer Gene Ther 20, 445–452 (2013). https://doi.org/10.1038/cgt.2013.39

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