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

Author

Listed:
  • 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
    Mayo Clinic)

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.

Suggested Citation

  • 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 & Dile, 2020. "Oncolytic virus-derived type I interferon restricts CAR T cell therapy," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17011-z
    DOI: 10.1038/s41467-020-17011-z
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    Cited by:

    1. Irene Andreu-Saumell & Alba Rodriguez-Garcia & Vanessa Mühlgrabner & Marta Gimenez-Alejandre & Berta Marzal & Joan Castellsagué & Fara Brasó-Maristany & Hugo Calderon & Laura Angelats & Salut Colell &, 2024. "CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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