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

Publication ,  Journal Article
Evgin, L; Huff, AL; Wongthida, P; Thompson, J; Kottke, T; Tonne, J; Schuelke, M; Ayasoufi, K; Driscoll, CB; Shim, KG; Reynolds, P; Monie, DD ...
Published in: Nat Commun
June 24, 2020

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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 24, 2020

Volume

11

Issue

1

Start / End Page

3187

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Spleen
  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Receptor, Interferon alpha-beta
  • Oncolytic Viruses
  • Oncolytic Virotherapy
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Evgin, L., Huff, A. L., Wongthida, P., Thompson, J., Kottke, T., Tonne, J., … Vile, R. (2020). Oncolytic virus-derived type I interferon restricts CAR T cell therapy. Nat Commun, 11(1), 3187. https://doi.org/10.1038/s41467-020-17011-z
Evgin, Laura, Amanda L. Huff, Phonphimon Wongthida, Jill Thompson, Tim Kottke, Jason Tonne, Matthew Schuelke, et al. “Oncolytic virus-derived type I interferon restricts CAR T cell therapy.Nat Commun 11, no. 1 (June 24, 2020): 3187. https://doi.org/10.1038/s41467-020-17011-z.
Evgin L, Huff AL, Wongthida P, Thompson J, Kottke T, Tonne J, et al. Oncolytic virus-derived type I interferon restricts CAR T cell therapy. Nat Commun. 2020 Jun 24;11(1):3187.
Evgin, Laura, et al. “Oncolytic virus-derived type I interferon restricts CAR T cell therapy.Nat Commun, vol. 11, no. 1, June 2020, p. 3187. Pubmed, doi: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. Oncolytic virus-derived type I interferon restricts CAR T cell therapy. Nat Commun. 2020 Jun 24;11(1):3187.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 24, 2020

Volume

11

Issue

1

Start / End Page

3187

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Spleen
  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Receptor, Interferon alpha-beta
  • Oncolytic Viruses
  • Oncolytic Virotherapy
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice