Details

Autor(en) / Beteiligte

• Castro, M.G
• Löwenstein, P.R
• Dewey, R. A
• Morrissey, G
• Cowsill, C. M
• Stone, D
• Bolognani, F
• Dodd, N.J.F
• Southgate, T. D
• Klatzmann, D
• Lassmann, H

Titel

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

Ist Teil von

• Nature medicine, 1999-11, Vol.5 (11), p.1256-1263

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

1999

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.