Oncolytic effects of a novel influenza A virus expressing interleukin-15 from the NS reading frame.

PloS One
Marijke van RikxoortJindrich Cinatl

Abstract

Oncolytic influenza A viruses with deleted NS1 gene (delNS1) replicate selectively in tumour cells with defective interferon response and/or activated Ras/Raf/MEK/ERK signalling pathway. To develop a delNS1 virus with specific immunostimulatory properties, we used an optimised technology to insert the interleukin-15 (IL-15) coding sequence into the viral NS gene segment (delNS1-IL-15). DelNS1 and delNS1-IL-15 exerted similar oncolytic effects. Both viruses replicated and caused caspase-dependent apoptosis in interferon-defective melanoma cells. Virus replication was required for their oncolytic activity. Cisplatin enhanced the oncolytic activity of delNS1 viruses. The cytotoxic drug increased delNS1 replication and delNS1-induced caspase-dependent apoptosis. Interference with MEK/ERK signalling by RNAi-mediated depletion or the MEK inhibitor U0126 did not affect the oncolytic effects of the delNS1 viruses. In oncolysis sensitive melanoma cells, delNS1-IL-15 (but not delNS1) infection resulted in the production of IL-15 levels ranging from 70 to 1140 pg/mL in the cell culture supernatants. The supernatants of delNS1-IL-15-infected (but not of delNS1-infected) melanoma cells induced primary human natural killer cell-mediated lysi...Continue Reading

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Citations

Nov 6, 2013·Immunotherapy·Matthew J Atherton, Brian D Lichty
Apr 9, 2016·Oncoimmunology·Jonathan PolLorenzo Galluzzi
Jun 8, 2015·Cancer Immunology, Immunotherapy : CII·Manisha Singh, Willem W Overwijk
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Aug 24, 2017·Viruses·Daniel N SantiagoHeiko Enderling
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Jun 2, 2017·The Open Virology Journal·Tiantian ZhangKarim Essani
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May 7, 2016·BMC Medicine·Sofia FarkonaIvan M Blasutig
Feb 2, 2018·Future Virology·Justin MarounStephen Russell
Jul 6, 2014·Nature Reviews. Cancer·Brian D LichtyJohn C Bell
Jul 20, 2018·Veterinary Research·Yuguang FuGeorg Herrler

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Methods Mentioned

BETA
transgenic
flow cytometry
Transfection
ELISA

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