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, Richard Vile

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number3187
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Oncolytic virus-derived type I interferon restricts CAR T cell therapy'. Together they form a unique fingerprint.

  • Cite this

    Evgin, L., Huff, A. L., Wongthida, P., Thompson, J., Kottke, T., Tonne, J., Schuelke, M., Ayasoufi, K., Driscoll, C. B., Shim, K. G., Reynolds, P., Monie, D. D., Johnson, A. J., Coffey, M., Young, S. L., Archer, G., Sampson, J., Pulido, J., Perez, L. S., & Vile, R. (2020). Oncolytic virus-derived type I interferon restricts CAR T cell therapy. Nature communications, 11(1), [3187]. https://doi.org/10.1038/s41467-020-17011-z