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Cytidine Deaminase in Myeloprotective Gene Therapy

Authors
  • Lachmann, Nico
  • Brennig, Sebastian
  • Moritz, Thomas
Type
Book
Journal
Gene Therapy of Cancer
Publication Date
Jan 01, 2014
Pages
423–440
Identifiers
DOI: 10.1016/B978-0-12-394295-1.00029-9
ISBN: 978-0-12-394295-1
Source
Elsevier
Keywords
License
Unknown

Abstract

Gene transfer of drug-resistance (CTX-R) genes can be utilized to protect the hematopoietic system from the toxicity of anticancer chemotherapy, and this concept recently has been proven for O6-methylguanine methyltransferase in the context of temozolomide therapy of glioblastoma patients. Given its protection capacity against such relevant drugs as arabinoside cytosine, gemcitabine, or 5-azacytidin and the highly hematopoiesis-specific toxicity profile of several of these agents, cytidine deaminase (CDD) represents another particularly interesting candidate CTX-R gene. Recently, our group established the myeloprotective capacity of CDD gene transfer in a number of murine transplant studies. Although these studies also have highlighted the problems and risks still associated with CDD gene transfer, such as lymphotoxicity, lack of long-term in vivo selection, insertional mutagenesis, or inadvertent transduction of malignant cells, these may be overcome by recent developments in the field, such as safety-improved self-inactivating vector constructs, regulated transgene expression systems, or novel CTX-R genes.

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