Human bone marrow-derived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Δ24-RGD to human gliomas

Raymund L. Yong, Naoki Shinojima, Juan Fueyo, Joy Gumin, Giacomo G. Vecil, Frank C. Marini, Oliver Bogler, Michael Andreeff, Frederick F. Lang

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Δ24-RGD is an infectivity-augmented, conditionally replicative oncolytic adenovirus with significant antiglioma effects. Although intratumoral delivery of Δ24-RGD may be effective, intravascular delivery would improve successful application in humans. Due to their tumor tropic properties, we hypothesized that human mesenchymal stem cells (hMSC) could be harnessed as intravascular delivery vehicles of Δ24-RGD to human gliomas. To assess cellular events, green fluorescent protein-labeled hMSCs carrying Δ24-RGD (hMSC-Δ24) were injected into the carotid artery of mice harboring orthotopic U87MG or U251-V121 xenografts and brain sections were analyzed by immunofluorescence for green fluorescent protein and viral proteins (E1A and hexon) at increasing times. hMSC-Δ24 selectively localized to glioma xenografts and released Δ24-RGD, which subsequently infected glioma cells. To determine efficacy, mice were implanted with luciferase-labeled glioma xenografts, treated with hMSC-Δ24 or controls, and imaged weekly by bioluminescence imaging. Analysis of tumor size by bioluminescence imaging showed inhibition of glioma growth and eradication of tumors in hMSC-Δ24-treated animals compared with controls (P < 0.0001). There was an increase in median survival from 42 days in controls to 75.5 days in hMSC-Δ24-treated animals (P < 0.0001) and an increase in survival beyond 80 days from 0% to 37.5%, respectively. We conclude that intra-arterially delivered hMSC-Δ24 selectively localize to human gliomas and are capable of delivering and releasing Δ24-RGD into the tumor, resulting in improved survival and tumor eradication in subsets of mice.

Original languageEnglish (US)
Pages (from-to)8932-8940
Number of pages9
JournalCancer Research
Volume69
Issue number23
DOIs
StatePublished - Dec 1 2009

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yong, R. L., Shinojima, N., Fueyo, J., Gumin, J., Vecil, G. G., Marini, F. C., Bogler, O., Andreeff, M., & Lang, F. F. (2009). Human bone marrow-derived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Δ24-RGD to human gliomas. Cancer Research, 69(23), 8932-8940. https://doi.org/10.1158/0008-5472.CAN-08-3873