Oncolytic virus therapy for malignant glioma using G47Δ

Abstract

G47Δ is a third-generation oncolytic herpes simplex virus type 1（HSV-1）that has triple mutations created in the HSV-1 genome deletions in both copies of the γ34.5 gene, an insertion of the E. coli lacZ gene in the ICP6 locus, and a deletion of the α47 gene. G47Δ shows a high efficacy for theating malignant glioma as well as for other solid cancers, because of its enhanced tumor-selective viral replication and cell killing, and efficient induction of systemic antitumor immunity. The first-in-man clinical trial in recurrent glioblastoma patients that lasted 5 years from 2009 proved the safety of G47Δ when injected into the brain tumor stereotactically twice within 2 weeks. Some patients showed a long-term efficacy that seemed to have been caused by the induction of specific antitumor immunity rather than the direct oncolytic activity of G47Δ. In the phaseⅡ trial that started in 2015, a patient must have glioblastoma with a single residual or recurrent tumor after initial radiation therapy, and a KPS of 60% or higher. The eligible patients receive repeated stereotactic injections with G47Δ every 4 weeks, 6 injections being the maximum total. The efficacy of G47Δ will be evaluated using a one-year survival rate as the primary endpoint. We believe G47Δ will become a standard treatment for all malignant glioma in Japan in the near future.