Pre-existing immunity to oncolytic virus potentiates its immunotherapeutic efficacy Journal Article

Authors: Ricca, J. M.; Oseledchyk, A.; Walther, T.; Liu, C.; Mangarin, L.; Merghoub, T.; Wolchok, J. D.; Zamarin, D.
Article Title: Pre-existing immunity to oncolytic virus potentiates its immunotherapeutic efficacy
Abstract: Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs. Pre-existing anti-viral immunity presents a challenge for systemically administered oncolytic viruses, but its effects on the intratumoral oncolytic immunotherapy are not well defined. Ricca and colleagues find that pre-existing immunity to intratumoral oncolytic Newcastle Disease Virus does not reduce, but rather potentiates its therapeutic efficacy through enhanced anti-tumor immune response. © 2018 The Author(s)
Keywords: cancer immunotherapy; oncolytic virus; newcastle disease virus; ndv; tumor immunology; immuno-oncology; pre-existing immunity
Journal Title: Molecular Therapy
Volume: 26
Issue: 4
ISSN: 1525-0016
Publisher: Nature Publishing Group  
Date Published: 2018-04-04
Start Page: 1008
End Page: 1019
Language: English
DOI: 10.1016/j.ymthe.2018.01.019
PROVIDER: scopus
PUBMED: 29478729
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    669 Wolchok
  2. Taha Merghoub
    209 Merghoub
  3. Dmitriy Zamarin
    56 Zamarin
  4. Cailian Liu
    36 Liu
  5. Jacob M Ricca
    14 Ricca