Lysis-independent potentiation of immune checkpoint blockade by oncolytic virus Journal Article


Authors: Oseledchyk, A.; Ricca, J. M.; Gigoux, M.; Ko, B.; Redelman-Sidi, G.; Walther, T.; Liu, C.; Iyer, G.; Merghoub, T.; Wolchok, J. D.; Zamarin, D.
Article Title: Lysis-independent potentiation of immune checkpoint blockade by oncolytic virus
Abstract: 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. ©Oseledchyk et al.
Keywords: bladder cancer; immunotherapy; pd-1; lysis; ndv
Journal Title: Oncotarget
Volume: 9
Issue: 47
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2018-06-19
Start Page: 28702
End Page: 28716
Language: English
DOI: 10.18632/oncotarget.25614
PROVIDER: scopus
PMCID: PMC6033351
PUBMED: 29983890
DOI/URL:
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    905 Wolchok
  2. Taha Merghoub
    365 Merghoub
  3. Dmitriy Zamarin
    202 Zamarin
  4. Gopakumar Vasudeva Iyer
    352 Iyer
  5. Cailian Liu
    60 Liu
  6. Jacob M Ricca
    16 Ricca
  7. Mathieu Gigoux
    23 Gigoux
  8. Brian Ko
    1 Ko