Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy

Cancer Lett. 2021 Jul 1;509:26-38. doi: 10.1016/j.canlet.2021.03.027. Epub 2021 Apr 2.


Oncolytic adenovirus-mediated gene therapy shows promise for cancer treatment; however, the systemic delivery of oncolytic adenovirus to tumors remains challenging. Recently, mesenchymal stem cells (MSCs) have emerged as potential vehicles for improving delivery. Yet, because the oncolytic adenovirus replicates in MSCs, balancing MSC viability with viral load is key to achieving optimal therapeutic effect. We thus developed an all-in-one Tet-on system that can regulate replication of oncolytic adenovirus. Then, we loaded the novel oncolytic adenovirus carrying interleukin (IL)-24 and/or Endostatin in human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) for glioma therapy. In vitro assays demonstrated that this novel oncolytic adenovirus could efficiently replicate and kill glioma cells while sparing normal cells. Moreover, doxycycline effectively regulated oncolytic adenovirus replication in the hUCB-MSCs. The doxycycline induction group with dual expression of IL-24 and Endostatin exhibited significantly greater antitumor effects than other groups in a xenograft model of glioma. Thus, this strategy for systemic delivery of oncolytic adenovirus with its oncolytic activity controlled by a Tet-on system is a promising method for achieving antitumor efficacy in glioma, especially for metastatic tumors.

Keywords: Conditionally replicating adenovirus; Endostatin; IL-24; MSC; Tet-on system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / therapy*
  • Brain Neoplasms / virology
  • Cell Death
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cord Blood Stem Cell Transplantation*
  • Endostatins / biosynthesis*
  • Endostatins / genetics
  • Female
  • Genetic Therapy*
  • Genetic Vectors
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / therapy*
  • Glioma / virology
  • Humans
  • Interleukins / biosynthesis*
  • Interleukins / genetics
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / virology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / growth & development
  • Tumor Burden
  • Virus Replication
  • Xenograft Model Antitumor Assays


  • Endostatins
  • Interleukins
  • interleukin-24