Oncolytic virus-derived type I interferon restricts CAR T cell therapy

Laura Evgin, Amanda L. Huff, Phonphimon Wongthida, Jill Thompson, Tim Kottke, Jason Tonne, Matthew Schuelke, Katayoun Ayasoufi, Christopher B. Driscoll, Kevin G. Shim, Pierce Reynolds, Dileep D. Monie, Aaron J. Johnson, Matt Coffey, Sarah L. Young, Gary Archer, John Sampson, Jose Pulido, Luis Sanchez Perez and Richard Vile ()
Additional contact information
Laura Evgin: Mayo Clinic
Amanda L. Huff: Mayo Clinic
Phonphimon Wongthida: Mayo Clinic
Jill Thompson: Mayo Clinic
Tim Kottke: Mayo Clinic
Jason Tonne: Mayo Clinic
Matthew Schuelke: Mayo Clinic
Katayoun Ayasoufi: Mayo Clinic
Christopher B. Driscoll: Mayo Clinic
Kevin G. Shim: Mayo Clinic
Pierce Reynolds: Mayo Clinic
Dileep D. Monie: Mayo Clinic
Aaron J. Johnson: Mayo Clinic
Matt Coffey: Oncolytics Biotech Incorporated
Sarah L. Young: University of Otago
Gary Archer: Duke University
John Sampson: Duke University
Jose Pulido: Mayo Clinic
Luis Sanchez Perez: Duke University
Richard Vile: Mayo Clinic

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNβ. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17011-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17011-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17011-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().