Cytokine-induced killer cell delivery enhances the antitumor activity of oncolytic reovirus

PLoS One. 2017 Sep 18;12(9):e0184816. doi: 10.1371/journal.pone.0184816. eCollection 2017.

Abstract

Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery. In this study, CIK cells were successfully loaded with reovirus ex vivo, and viral replication was limited in CIK cells. Confocal microscopy and flow cytometry demonstrated that CIK cells retained reovirus on the surface. Moreover, CIK cells could promote reovirus infection of tumor cells in the presence of neutralizing antibodies; meanwhile, cytotoxicity of CIK cells was increased after loading with reovirus. These findings support further investigation of reovirus and CIK combination for antitumor therapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokine-Induced Killer Cells / immunology*
  • Humans
  • Immunity, Cellular*
  • Mammalian orthoreovirus 3 / physiology*
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Oncolytic Viruses / physiology*
  • Virus Replication / immunology*

Grants and funding

This work was supported by funds from National Natural Science Foundation of China (grant number 81360346, http://www.nsfc.gov.cn/); The Social Developmental Research Foundation of Guizhou Province [grant number SY(2012)3094, http://www.gzpopss.gov.cn/]; and Guizhou Province's Science and Technology Major Project, Qian-J-Zhong (grant number [2015]2003, http://kjzdzx.gzste.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.