Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects

Mol Ther. 2013 Mar;21(3):620-8. doi: 10.1038/mt.2012.257. Epub 2012 Dec 11.

Abstract

The combination of an oncolytic virus, that directly destroys tumor cells and mediates an acute immune response, with an immune cell therapy, capable of further enlisting and enhancing the host immune response, has the potential to create a potent therapeutic effect. We have previously developed several strategies for optimizing the delivery of oncolytic vaccinia virus vectors to their tumor targets, including the use of immune cell-based carrier vehicles and the incorporation of mutations that increase production of the enveloped form of vaccinia (extracellular enveloped viral (EEV)) that is better adapted to spread within a host. Here, we initially combine these approaches to create a novel therapeutic, consisting of an immune cell (cytokine-induced killer, CIK) preloaded with an oncolytic virus that is EEV enhanced. This resulted in direct interaction between the viral and immune cell components with each assisting the other in directing the therapy to the tumor and so enhancing the antitumor effects. This effect could be further improved through CCL5 expression from the virus. The resulting multicomponent therapy displays the ability for synergistic crosstalk between components, so significantly enhancing tumor trafficking and antitumor effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Cytokine-Induced Killer Cells / immunology*
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / physiology
  • Vaccinia virus / genetics*
  • Vaccinia virus / physiology
  • Virus Replication

Substances

  • Antineoplastic Agents
  • Chemokine CCL5