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Sci Transl Med. 2017 Sep 20;9(408). pii: eaan4220. doi: 10.1126/scitranslmed.aan4220.

Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs.

Author information

1
Department of Neurosurgery, Duke University School of Medicine, Durham, NC 27710, USA.
2
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
3
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
4
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
5
Department of Neurosurgery, Duke University School of Medicine, Durham, NC 27710, USA. smita.nair@duke.edu grome001@mc.duke.edu.
6
Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. smita.nair@duke.edu grome001@mc.duke.edu.

Abstract

Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer immunotherapy potential of the recombinant poliovirus/rhinovirus chimera PVSRIPO. PVSRIPO is currently in clinical trials against recurrent World Health Organization grade IV malignant glioma, a notoriously treatment-refractory cancer. Cytopathogenic infection of neoplastic cells releases the proteome and exposes pathogen- and damage-associated molecular patterns. At the same time, sublethal infection of antigen-presenting cells, such as dendritic cells and macrophages, yields potent, sustained type I interferon-dominant activation in an immunosuppressed microenvironment and promotes the development of tumor antigen-specific T cell responses in vitro and antitumor immunity in vivo. PVSRIPO's immune adjuvancy stimulates canonical innate anti-pathogen inflammatory responses within the tumor microenvironment that culminate in dendritic cell and T cell infiltration. Our findings provide mechanistic evidence that PVSRIPO functions as a potent intratumor immune adjuvant that generates tumor antigen-specific cytotoxic T lymphocyte responses.

Comment in

PMID:
28931654
PMCID:
PMC6034685
DOI:
10.1126/scitranslmed.aan4220
[Indexed for MEDLINE]
Free PMC Article

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