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Development of measles virus-based shielded oncolytic vectors: suitability of other paramyxovirus glycoproteins

Cancer Gene Therapy volume 20, pages 109–116 (2013)Cite this article

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Abstract

Antibody-mediated neutralization may interfere with the efficacy of measles virus (MV) oncolysis. To circumvent vector neutralization, we sought to exchange the envelope glycoproteins, hemagglutinin (H) and fusion (F), with those from the non-crossreactive Tupaia paramyxovirus (TPMV). To sustain efficient particle assembly, we generated hybrid glycoproteins with the MV cytoplasmic tails and the TPMV ectodomains. Hybrid F proteins that partially retained fusion function, and hybrid H proteins that retained fusion support activity, were generated. However, when used in combination, the hybrid proteins did not support membrane fusion. An alternative strategy was developed based on a hybrid F protein and a truncated H protein that supported cell–cell fusion. A hybrid virus expressing these two proteins was rescued, and was able to spread by cell fusion; however, it was only capable of producing minimal amounts of particles. Lack of specific interactions between the matrix and the H protein, in combination with suboptimal F-protein processing and inefficient glycoprotein transport in the rescue cells, accounted for inefficient particle production. Ultimately, this interferes with applications for oncolytic virotherapy. Alternative strategies for the generation of shielded MV are discussed.

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Acknowledgements

We thank Dr Christoph Springfeld for providing the TPMV-Fecto antibody and helpful insights into previously attempted envelope exchanges. We thank Dr Stephen Russell for providing the Vero-αHis cell line, and Dr Patricia Devaux for numerous helpful discussions. This work was supported by NIH RO1 CA 139389. The salary of AWH was provided, in part, by the Mayo Graduate School.

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  1. A W Hudacek

    Present address: 2Current address: Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.,

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  1. Department of Molecular Medicine, Virology and Gene Therapy Track, Mayo Clinic College of Medicine, Rochester, MN, USA

    A W Hudacek, C K Navaratnarajah & R Cattaneo

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  1. A W Hudacek
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  2. C K Navaratnarajah
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Correspondence to R Cattaneo.

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Hudacek, A., Navaratnarajah, C. & Cattaneo, R. Development of measles virus-based shielded oncolytic vectors: suitability of other paramyxovirus glycoproteins. Cancer Gene Ther 20, 109–116 (2013). https://doi.org/10.1038/cgt.2012.92

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