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Clinical trials with retrovirus mediated gene therapy--what have we learned?

Nikolai G Rainov1, Huan Ren

  • 1Department of Neurological Science, University of Liverpool, Liverpool, UK. rainov@liv.ac.uk

Journal of Neuro-Oncology
|December 20, 2003
PubMed

Insights

Retrovirus (RV) gene therapy showed promise for malignant glioma but failed in a phase III trial due to low transduction rates. Lessons learned are guiding development of new brain tumor gene therapy vectors.

Area of Science:

  • Oncolytic virotherapy
  • Gene therapy for brain tumors
  • Retroviral vector applications

Background:

  • Retrovirus (RV) vectors were early candidates for cancer gene therapy, particularly for malignant glioma.
  • Early studies demonstrated RV's ability to transduce glioma cells and mediate tumor cell killing via transgenes.
  • Phase I/II trials in recurrent glioma showed RV gene therapy was safe and somewhat effective.

Purpose of the Study:

  • To evaluate the efficacy and safety of Retrovirus (RV) mediated gene therapy in malignant glioma.
  • To identify limitations and shortcomings of RV gene therapy strategies in brain tumor treatment.

Main Methods:

  • In vitro and in vivo experiments using RV vectors for gene transduction in glioma models.
  • Clinical trials (Phase I, II, and III) involving patients with malignant glioma, including a randomized phase III study.
  • Analysis of tumor cell transduction rates and biological effects of transgene/prodrug systems.

Main Results:

  • RV gene therapy demonstrated feasibility and some efficacy in early-phase recurrent glioma trials.
  • A phase III trial in primary malignant glioma did not show significant improvements in progression-free or overall survival.
  • Low in vivo tumor cell transduction rates were identified as a potential reason for trial failure.

Conclusions:

  • Retrovirus gene therapy for malignant glioma has limitations, including insufficient tumor cell transduction.
  • The choice of transgene/prodrug and vector delivery methods significantly impacts therapeutic outcomes.
  • Insights from RV trials are crucial for designing improved viral vector systems for future brain tumor gene therapy.

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