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

doi:10.1038/s41467-020-17011-z

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 journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Article number	3187
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17011-z
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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), Article 3187. https://doi.org/10.1038/s41467-020-17011-z

Evgin, L, Huff, AL, Wongthida, P, Thompson, J, Kottke, T, Tonne, J, Schuelke, M, Ayasoufi, K, Driscoll, CB, Shim, KG, Reynolds, P, Monie, DD, Johnson, AJ, Coffey, M, Young, SL, Archer, G, Sampson, J, Pulido, J, Perez, LS & Vile, R 2020, 'Oncolytic virus-derived type I interferon restricts CAR T cell therapy', Nature communications, vol. 11, no. 1, 3187. https://doi.org/10.1038/s41467-020-17011-z

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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.",

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AU - Schuelke, Matthew

AU - Ayasoufi, Katayoun

AU - Driscoll, Christopher B.

AU - Shim, Kevin G.

AU - Reynolds, Pierce

AU - Monie, Dileep D.

AU - Johnson, Aaron J.

AU - Coffey, Matt

AU - Young, Sarah L.

AU - Archer, Gary

AU - Sampson, John

AU - Pulido, Jose

AU - Perez, Luis Sanchez

AU - Vile, Richard

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

Abstract

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