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Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.

Publication ,  Journal Article
Mosaheb, MM; Dobrikova, EY; Brown, MC; Yang, Y; Cable, J; Okada, H; Nair, SK; Bigner, DD; Ashley, DM; Gromeier, M
Published in: Nat Commun
January 27, 2020
Published version (DOI) Link to item

Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models.

Duke Scholars

Michael Brown
Author Michael Brown Neurosurgery, Neuro-Oncology
Smita K Nair
Author Smita K Nair Surgery, Surgical Sciences
Darell Doty Bigner
Author Darell Doty Bigner Neurosurgery
David Michael Ashley
Author David Michael Ashley Neurosurgery
Matthias Gromeier
Author Matthias Gromeier Neurosurgery, Neuro-Oncology
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Published In

Nat Commun

DOI

10.1038/s41467-019-13939-z

EISSN

2041-1723

Publication Date

January 27, 2020

Volume

11

Issue

1

Start / End Page

524

Location

England

Related Subject Headings

  • Poliovirus
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Interferon Type I
  • Immunotherapy
  • Immunity, Innate
  • Humans
  • Hela Cells
  • HeLa Cells
 

Citation

APA
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ICMJE
MLA
NLM
Mosaheb, M. M., Dobrikova, E. Y., Brown, M. C., Yang, Y., Cable, J., Okada, H., … Gromeier, M. (2020). Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity. Nat Commun, 11(1), 524. https://doi.org/10.1038/s41467-019-13939-z
Mosaheb, Mubeen M., Elena Y. Dobrikova, Michael C. Brown, Yuanfan Yang, Jana Cable, Hideho Okada, Smita K. Nair, Darell D. Bigner, David M. Ashley, and Matthias Gromeier. “Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.” Nat Commun 11, no. 1 (January 27, 2020): 524. https://doi.org/10.1038/s41467-019-13939-z.
Mosaheb MM, Dobrikova EY, Brown MC, Yang Y, Cable J, Okada H, et al. Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity. Nat Commun. 2020 Jan 27;11(1):524.
Mosaheb, Mubeen M., et al. “Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.” Nat Commun, vol. 11, no. 1, Jan. 2020, p. 524. Pubmed, doi:10.1038/s41467-019-13939-z.
Mosaheb MM, Dobrikova EY, Brown MC, Yang Y, Cable J, Okada H, Nair SK, Bigner DD, Ashley DM, Gromeier M. Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity. Nat Commun. 2020 Jan 27;11(1):524.

Published In

Nat Commun

DOI

10.1038/s41467-019-13939-z

EISSN

2041-1723

Publication Date

January 27, 2020

Volume

11

Issue

1

Start / End Page

524

Location

England

Related Subject Headings

  • Poliovirus
  • Mice, Inbred C57BL
  • Mice
  • Melanoma
  • Interferon Type I
  • Immunotherapy
  • Immunity, Innate
  • Humans
  • Hela Cells
  • HeLa Cells