[Oncolytic virotherapy using replication-competent herpes simplex viruses]

Oncolytic virotherapy using replication-competent viruses has attracted us as a new modality for cancer treatment. The fundamental concept of oncolytic virotherapy is that the viruses selectively replicate in and lyse tumor cells. Since 1997, numbers of clinical trials have been done in over 500 cancer patients. However, the results of those trials have been disappointing in most cases. We have isolated a spontaneously occurring herpes simplex virus type 1 mutant, designated HF10, which efficiently replicates and induces cell fusion in most transformed cells, but is highly attenuated in mice. HF10 has a number of deletions and insertions in the genome, resulting in the lack of the functional expression of UL43, UL49.5, UL55, UL56 and latency-associated transcripts. We have found that HF10 can be used as an oncolytic virus for treatment of malignant tumors in various animal models. Clinical trials have shown that intratumoral injection of HF10 can induce extensive tumor cell death in patients with recurrent breast cancer and head and neck squamous cell carcinoma without significant adverse effects. HF10 is a promising agent for use in oncolytic virotherapy in non-central nervous system malignancies.