Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: Targeted delivery of the therapeutic payload in an orthotopic brain tumor model

B. Thaci, A. U. Ahmed, I. V. Ulasov, A. L. Tobias, Y. Han, K. S. Aboody, M. S. Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Oncolytic virotherapy is a promising novel therapy for glioblastoma that needs to be optimized before introduced to clinic. The targeting of conditionally replicating adenoviruses (CRAds) can be improved by relying on the tumor-tropic properties of neural stem cells (NSCs). Here, we report the characterization of an FDA approved NSC, HB1.F3-CD, as a cell carrier for CRAd-S-pk7, a glioma-tropic oncolytic adenovirus. We show that NSCs replicate and release infectious CRAd-S-pk7 progeny capable of lysing glioma cell lines. Moreover, ex-vivo-loaded NSCs, injected intracranially in nude mice bearing human glioma xenografts (i) retained their tumor tropism, (ii) continued to replicate CRAd-S-pk7 for more than a week after reaching the tumor site and (iii) successfully handed off CRAd-S-pk7 to glioma cells in vivo. Delivery via carrier cells reduced non-specific adenovirus distribution in the mouse brain. Moreover, we assessed biodistribution of loaded NSCs after intracranial injection in animal models semi-permissive to adenovirus replication, the Syrian hamster and cotton rat. NSCs did not migrate to distant organs and high levels of CRAd-S-pk7 DNA were observed only in the injected hemisphere. In conclusion, this optimized carrier system, with high efficiency of adenovirus delivery and minimal systemic toxicity, poses considerable advantages for anti-glioma oncolytic virotherapy.

Original languageEnglish (US)
Pages (from-to)431-442
Number of pages12
JournalCancer Gene Therapy
Volume19
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Adenovirus
  • carrier
  • cotton rat
  • hamster
  • neural stem cell
  • oncolytic virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: Targeted delivery of the therapeutic payload in an orthotopic brain tumor model'. Together they form a unique fingerprint.

Cite this