Pre-existing Immunity to Oncolytic Virus Potentiates Its Immunotherapeutic Efficacy

Mol Ther. 2018 Apr 4;26(4):1008-1019. doi: 10.1016/j.ymthe.2018.01.019. Epub 2018 Jan 31.


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.

Keywords: NDV; Newcastle Disease Virus; cancer immunotherapy; immuno-oncology; oncolytic virus; pre-existing immunity; tumor immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression
  • Genetic Therapy / adverse effects*
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • Humans
  • Injections, Intralesional
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Melanoma, Experimental
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Newcastle disease virus / genetics
  • Newcastle disease virus / immunology
  • Oncolytic Virotherapy / adverse effects*
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transgenes
  • Treatment Outcome
  • Xenograft Model Antitumor Assays