Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: Implications for clinical trials

10.1038/15207 ◽  
1999 ◽  
Vol 5 (11) ◽  
pp. 1256-1263 ◽  
Author(s):  
R. A. Dewey ◽  
G. Morrissey ◽  
C. M. Cowsill ◽  
D. Stone ◽  
F. Bolognani ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Brain Inflammation ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Kinase Expression

scholarly journals Chronic Brain Inflammation and Persistent Herpes Simplex Virus 1 Thymidine Kinase Expression in Survivors of Syngeneic Glioma Treated by Adenovirus-Mediated Gene Therapy: Implications for Clinical Trials

1999 ◽  
Vol 7 (6) ◽  
pp. E13
Author(s):  
William T. Couldwell
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Brain Inflammation ◽  
Herpes Simplex Virus 1 ◽  
Glioma Growth ◽  
Simplex Virus

The long-term consequences of adenovirus-mediated conditional cytotoxic gene therapy for gliomas remain uncharacterized. We report here detection of active brain inflammation 3 months after successful inhibition of syngeneic glioma growth. The inflammatory infiltrate consisted of activated macrophages/microglia and astrocytes, and T lymphocytes positive for leucosyalin, CD3 and CD8, and included secondary demyelination. We detected strong widespread herpes simplex virus 1 thymidine kinase immunoreactivity and vector genomes throughout large areas of the brain. Thus, patient evaluation and the design of clinical trials in ongoing and future gene therapy for brain glioblastoma must address not only tumor-killing efficiency, but also long-term active brain inflammation, loss of myelin fibers and persistent transgene expression.

scholarly journals Hybrid plasmids containing an active thymidine kinase gene of Herpes simplex virus 1

1979 ◽  
Vol 7 (4) ◽  
pp. 859-878 ◽  
Author(s):  
N.M. Wilkie ◽  
J.B. Clements ◽  
W. Boll ◽  
N. Mantei ◽  
D. Lonsdale ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Thymidine Kinase Gene ◽  
Herpes Simplex Virus 1 ◽  
Kinase Gene ◽  
Simplex Virus
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