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Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection

Cancer Gene Therapy volume 21, pages 24–30 (2014)Cite this article

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Abstract

Newcastle disease virus (NDV) is a naturally occurring oncolytic virus with clinically proven efficacy against several human tumor types. Selective replication in and killing of tumor cells by NDV is thought to occur because of differences in innate immune responses between normal and tumor cells. In our effort to develop oncolytic virotherapy with NDV for patients with pancreatic cancer, we evaluated the responses to NDV infection and interferon (IFN) treatment of 11 different established human pancreatic adenocarcinoma cell lines (HPACs). Here we show that all HPACs were susceptible to NDV. However, this NDV infection resulted in different replication kinetics and cytotoxic effects. Better replication resulted in more cytotoxicity. No correlation was observed between defects in the IFN pathways and NDV replication or NDV-induced cytotoxicity. IFN production by HPACs after NDV infection differed substantially. Pretreatment of HPACs with IFN resulted in diminished NDV replication and decreased the cytotoxic effects in most HPACs. These findings suggest that not all HPACs have functional defects in the innate immune pathways, possibly resulting in resistance to oncolytic virus treatment. These data support the rationale for designing recombinant oncolytic NDVs with optimized virulence that should likely contain an antagonist of the IFN pathways.

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Acknowledgements

This study was supported by the Virgo consortium, funded by the Dutch government project number FES0908 and by the Netherlands Genomics Initiative (NGI) project number 050-060-452.

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Authors and Affiliations

  1. Department of Surgery, Erasmus MC, Rotterdam, The Netherlands

    P R A Buijs & C H J van Eijck

  2. Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands

    L J Hofland

  3. Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands

    R A M Fouchier & B G van den Hoogen

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Correspondence to B G van den Hoogen.

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Buijs, P., van Eijck, C., Hofland, L. et al. Different responses of human pancreatic adenocarcinoma cell lines to oncolytic Newcastle disease virus infection. Cancer Gene Ther 21, 24–30 (2014). https://doi.org/10.1038/cgt.2013.78

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