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
- 32581235
Electronic International Standard Serial Number (EISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/s41467-020-17011-z
Language
- eng
Conference Location
- England