Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma

The herpes simplex virus (HSV) ICP34.5 null mutant 1716 replicates selectiv ely in actively dividing cells and has been proposed as a potential treatme nt for cancer, particularly brain tumours. We present a clinical study to e valuate the safety of 1716 in patients with relapsed malignant glioma. Foll owing intratumoural inoculation of doses up to 10(5) p.f.u., there was no i nduction of encephalitis, no adverse clinical symptoms, and no reactivation of latent HSV. Of nine patients treated, four are currently alive and well 14-24 months after 1716 administration. This study demonstrates the feasib ility of using replication-competent HSV in human therapy.