Lysis-independent potentiation of immune checkpoint blockade by oncolytic virus Academic Article Article uri icon

Overview

MeSH Major

  • Genital Neoplasms, Female
  • Immunotherapy

abstract

  • ¬©Oseledchyk et al. Intratumoral therapy with oncolytic viruses is increasingly being explored as a strategy to potentiate an immune response against cancer, but it remains unknown whether such therapy should be restricted to cancers sensitive to virus-mediated lysis. Using Newcastle Disease Virus (NDV) as a model, we explore immunogenic potential of an oncolytic virus in bladder cancer, where existing immunotherapy with PD-1 and PD-L1-targeting antibodies to date has shown suboptimal response rates. Infection of human and mouse bladder cancer cells with NDV resulted in immunogenic cell death, activation of innate immune pathways, and upregulation of MHC and PD-L1 in all tested cell lines, including the cell lines completely resistant to NDV-mediated lysis. In a bilateral flank NDV-lysis-resistant syngeneic murine bladder cancer model, intratumoral therapy with NDV led to an increase of immune infiltration in both treated and distant tumors and a shift from an inhibitory to effector T cell phenotype. Consequently, combination of intratumoral NDV with systemic PD-1 or CTLA-4 blockade led to improved local and abscopal tumor control and overall survival. These findings encourage future clinical trials combining intratumoral NDV therapy with systemic immunomodulatory agents and underscore the rationale for such treatments irrespective of tumor cell sensitivity to NDV-mediated lysis.

publication date

  • June 19, 2018

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.25614

PubMed ID

  • 29983890

Additional Document Info

start page

  • 28702

end page

  • 28716

volume

  • 9

number

  • 47