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Tomato thymidine kinase-based suicide gene therapy for malignant glioma-an alternative for Herpes Simplex virus-1 thymidine kinase.

Stedt, H; Samaranayake, H; Kurkipuro, J; Wirth, G; Slot Christiansen, Louise LU ; Vuorio, T; Määttä, A-M; Piskur, Jure LU and Ylä-Herttuala, S (2015) In Cancer Gene Therapy 22(3). p.130-137
Abstract
Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in... (More)
Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P<0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.Cancer Gene Therapy advance online publication, 23 January 2015; doi:10.1038/cgt.2014.76. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Gene Therapy
volume
22
issue
3
pages
130 - 137
publisher
Nature Publishing Group
external identifiers
  • pmid:25613481
  • wos:000352464100005
  • scopus:84927696120
ISSN
1476-5500
DOI
10.1038/cgt.2014.76
language
English
LU publication?
yes
id
1907429d-f639-4e2f-9602-f0bb124e0003 (old id 5039965)
date added to LUP
2015-02-26 13:38:38
date last changed
2017-07-23 03:32:17
@article{1907429d-f639-4e2f-9602-f0bb124e0003,
  abstract     = {Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P&lt;0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.Cancer Gene Therapy advance online publication, 23 January 2015; doi:10.1038/cgt.2014.76.},
  author       = {Stedt, H and Samaranayake, H and Kurkipuro, J and Wirth, G and Slot Christiansen, Louise and Vuorio, T and Määttä, A-M and Piskur, Jure and Ylä-Herttuala, S},
  issn         = {1476-5500},
  language     = {eng},
  number       = {3},
  pages        = {130--137},
  publisher    = {Nature Publishing Group},
  series       = {Cancer Gene Therapy},
  title        = {Tomato thymidine kinase-based suicide gene therapy for malignant glioma-an alternative for Herpes Simplex virus-1 thymidine kinase.},
  url          = {http://dx.doi.org/10.1038/cgt.2014.76},
  volume       = {22},
  year         = {2015},
}