Genetically-engineered human neural stem cells with rabbit carboxyl esterase can target CNS lymphoma

Anticancer Res. 2013 Dec;33(12):5335-42.

Abstract

Background: Despite advances in its treatment, CNS lymphoma remains a devastating disease. Taking advantage of the tumour-tropic properties of neural stem cells (NSCs) is a novel therapeutic strategy. To apply this strategy to the treatment of CNS lymphoma, we investigated the role of NSCs expressing carboxyl esterase (HB1.F3.CE), which activates irinotecan.

Materials and methods: In order to find in vitro bystander effects of engineered NSCs, we performed cell viability assays. In vivo, the HB1.F3.CE cells were injected into the brain of mice with orthotopic CNS lymphoma. Mice were then treated with irinotecan by systemic administration.

Results: The HB1.F3.CE cells significantly inhibited the growth of Raji cells with irinotecan treatment. In vivo, the HB1.F3.CE cells migrated into the tumour and significantly reduced tumour volume. In addition, survival of mice was prolonged by treatment with HB1.F3.CE and irinotecan.

Conclusion: Transplantation of human NSCs encoding CE into brain, combined with irinotecan therapy, may be an effective treatment regimen for CNS lymphoma.

Keywords: CNS lymphoma; Irinotecan; carboxyl esterase (CE); neural stem cells; rabbit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic
  • Base Sequence
  • Bystander Effect
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Carboxylesterase / genetics*
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / therapy*
  • DNA Primers
  • Genetic Engineering*
  • Humans
  • Irinotecan
  • Lymphoma / drug therapy
  • Lymphoma / pathology
  • Lymphoma / therapy*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / enzymology
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antineoplastic Agents, Phytogenic
  • DNA Primers
  • Irinotecan
  • Carboxylesterase
  • Camptothecin