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Clinical
Trials with Retrovirus Mediated Gene Therapy – what Have we Learned?
Nikolai
G. Rainov¹’²,
Huan Ren¹
¹Department
of Neurological Science, University of Liverpool, Liverpool, UK. ²The
Walton Centre for Neurology and Neurosurgery NHS Trust, Liverpool, UK
Retrovirus
(RV) has been one of the earliest recombinant vectors to be investigated in the
context of cancer gene therapy.
Experiments in cell culture and in animal brain tumor models have demonstrated
the feasibility of RV mediated gene transduction and killing of glioma cells by
toxicity generating transgenes.
Phase I and II clinical studies in patients with recurrent malignant glioma have
shown a favorable safety profile and some efficacy of RV mediated gene therapy.
On the other hand, a prospective randomized phase III clinical study of RV gene
therapy in primary malignant glioma failed to demonstrate significant extension
of the progression-free or overall survival times in RV treated patients.
The failure of this RV gene therapy study may be due to the low tumor cell
transduction rate observed in vivo.
The biological effects of the treatment may also heavily depend on the choice of
transgene/prodrug system and on the vector delivery methods.
Retrovirus
clinical trials in malignant glioma have nevertheless produced a substantial
amount of data and have contributed toward the identification of serious
shortcomings of the non-replicating virus vector gene therapy strategy.
Novel types of therapeutic virus vector systems are currently being designed and
new clinical protocols are being created based on the lessons learned from the
RV gene therapy trials in patients with malignant brain tumors.
Keywords:
clinical trials, gene therapy, retrovirus, thymidine kinase
Copyright
© 2003 Kluwer
Academic Publishers. All
rights reserved
Source: http://ipsapp009.kluweronline.com/content/getfile/5042/105/6/abstract.htm
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