Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase

S. H. Lim, S. A. Choi, J. Y. Lee, K. C. Wang, J. H. Phi, D. H. Lee, S. H. Song, J. H. Song, X. Jin, Hyunggee Kim, H. J. Lee, I. Lim, S. U. Kim, S. K. Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, P0.001) or CPT-11 only (median survival: 118 days, P0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.

Original languageEnglish
Pages (from-to)817-824
Number of pages8
JournalCancer Gene Therapy
Volume18
Issue number11
DOIs
Publication statusPublished - 2011 Nov 1

Keywords

  • carboxylesterase
  • gene-directed enzyme prodrug therapy
  • medulloblastoma
  • metastasis
  • neural stem cell
  • tumor tropism

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase'. Together they form a unique fingerprint.

  • Cite this

    Lim, S. H., Choi, S. A., Lee, J. Y., Wang, K. C., Phi, J. H., Lee, D. H., Song, S. H., Song, J. H., Jin, X., Kim, H., Lee, H. J., Lim, I., Kim, S. U., & Kim, S. K. (2011). Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase. Cancer Gene Therapy, 18(11), 817-824. https://doi.org/10.1038/cgt.2011.52