Active immunotherapy: oncolytic virus therapy using HSV-1.

Conditionally replicating herpes simplex viruses Type 1 (HSV-1) are promising therapeutic agents for glioma. They can replicate in situ, spread and exhibit oncolytic activity via a direct cytocidal effect. In addition, specific antitumor immunity is effectively induced in the course of oncolytic activities. G47Δ is a genetically engineered HSV-1 with triple mutations that realized augmented viral replication in tumor cells, strong induction of antitumor immunity and enhanced safety in normal tissues. A clinical trial of G47Δ in patients with recurrent glioblastoma has started in 2009. One of the advantages of HSV-1 is its capacity to incorporate large and/or multiple transgenes within the viral genome. In preclinical studies, "arming" of an oncolytic HSV-1 with transgenes encoding immunomodulatory molecules, such as interleukin 12, has been shown to greatly augment the efficacy of oncolytic HSV-1 therapy. Oncolytic virus therapy using HSV-1 may be a useful treatment for glioma that can also function as an efficient in situ tumor vaccination.