Research ArticleCancer

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

See allHide authors and affiliations

Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaan4220
DOI: 10.1126/scitranslmed.aan4220

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

A double virus’s double attack on cancer

Oncolytic viruses, which are optimized to kill cancer cells without harming the surrounding normal tissues, have gathered increasing interest in recent years. One such virus is PVSRIPO, an engineered hybrid of poliovirus and rhinovirus that cannot attack neurons but retains cytotoxicity in neoplastic cells, including glioma. Brown et al. determined that PVSRIPO stimulates anticancer immunity by two mechanisms: lysing tumor cells to release a mix of tumor and viral antigens, as well as sublethally infecting antigen-presenting cells and thereby stimulating an interferon-driven immune response in the tumor microenvironment.

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.

View Full Text