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Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies

Gene Therapy volume 14, pages 324–333 (2007)Cite this article

Abstract

Neutralizing antiviral antibodies (Abs) can hinder systemic virotherapy. Here, we used activated T cells as carriers to deliver oncolytic measles viruses (MV) to multiple myeloma xenografts in the presence of anti-MV antibodies (Abs). Virus-infected T cells expressing measles H/F fusogenic envelope glycoproteins could efficiently transfer MV infection by heterofusion, even after exposure to virus-inactivating anti-MV antisera. Severe-combined immunodeficiency (SCID) mice bearing subcutaneous or disseminated human myeloma xenografts were given MV-luciferase (MV-Luc) or MV-Luc-infected T cells intravenously. Indium111 labeling indicated that 1–2% of the virus-infected T cells trafficked to tumors. Preinfected T cells fused with tumor cells in vivo and transferred MV-Luc to tumor xenografts where intratumoral viral spread was monitored non-invasively using bioluminescent imaging. In mice passively immunized with high titers of measles immune serum, intravenous virus and cell delivery were both inhibited. Decreasing the amount of measles immune serum given to mice permitted tumor infection by virus-infected T cells and cell-free virus. In conclusion, virus-loaded T cells may facilitate systemic measles virotherapy in the presence of antiviral Abs and they warrant further investigation as potential MV cell carriers.

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Acknowledgements

This work was supported by the JARI Foundation for Myeloma Research and the Mayo Foundation.

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Authors and Affiliations

  1. Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN, USA

    H T Ong, K Hasegawa, S J Russell & K-W Peng

  2. Transfusion Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    A B Dietz

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  1. H T Ong
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  2. K Hasegawa
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  4. S J Russell
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Correspondence to K-W Peng.

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Ong, H., Hasegawa, K., Dietz, A. et al. Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies. Gene Ther 14, 324–333 (2007). https://doi.org/10.1038/sj.gt.3302880

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