ATTENUATED MULTI-MUTATED HERPES-SIMPLEX VIRUS-1 FOR THE TREATMENT OF MALIGNANT GLIOMAS

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 .