We have created a double mutant of the herpes simplex virus (HSV) type
1 (termed G207) with favourable properties for treating human maligna
nt brain tumours: replication-competence in glioblastoma cells (and ot
her dividing cells), attenuated neurovirulence, temperature sensitivit
y, ganciclovir hypersensitivity, and the presence of an easily detecta
ble histochemical marker. G207 has deletions at both gamma 34.5 (RL1)
loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207
kills human glioma cells in monolayer cultures. In nude mice harbouri
ng subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inocu
lation with G207 causes decreased tumour growth and/or prolonged survi
val. G207 is avirulent upon intracerebral inoculation of mice and HSV-
sensitive non-human primates. These results suggest that G207 should b
e considered for clinical evaluation in the treatment of glioblastomas
.