Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy.
Growing cells from human brain tumors have been treated in vitro and in vivo with murine therapeutic retroviral producer cells. The therapeutic retrovirus carried the potential suicide gene thymidine kinase (tk) from the herpes simplex virus (HSV). After a few days, in which a large proportion of the tumoral cells had the opportunity to acquire a copy of the retrovirus, treatment with ganciclovir was initiated and considered responsible for considerable cell death both in vitro and in vivo. The in vivo experiments were performed in five adult patients who had failed standard therapy and were expected to survive only a few weeks.
Izquierdo
M
M
Departamento de Biología Molecular/Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias (módulo-C-X), Universidad Autónoma de Madrid, Spain.
Martín
V
V
de Felipe
P
P
Izquierdo
J M
JM
Pérez-Higueras
A
A
Cortés
M L
ML
Paz
J F
JF
Isla
A
A
Blázquez
M G
MG
D016475:3T3 Cells; D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016923:Cell Death / Q000187:drug effects; D018920:Coculture Techniques; D005347:Fibroblasts; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D051381:Rats; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir