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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • June 24, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 3187 -

PubMed ID

  • 32581235

Pubmed Central ID

  • PMC7314766

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-17011-z


  • eng

Conference Location

  • England