Treatment of solid sarcomas in immunocompetent mice with novel, oncolytic herpes simplex viruses.

Abstract

Attenuated, replication-competent herpes simplex viruses (HSVs) have shown promise as antitumor agents for cancer therapy. In this study, we sought to develop a novel type of oncolytic HSV with more potent antitumor activity for use in localized malignant tumors. A new, attenuated multimutated HSV (termed HL) was developed, and then a highly metastatic murine fibrosarcoma cell line, NfSa Y83, was injected into the necks or flanks of immunocompetent C3H mice. The mice were treated with attenuated HSV mutants by intratumoral injection, and antitumor efficacy was assessed by measuring tumor dimensions and overall survival rates. Treatment with intratumoral injection of HL resulted in marked regression of tumors. In fact, roughly 75% of flank tumors and 50% of neck tumors were completely eradicated. A novel type of attenuated HSV recombinant HL demonstrated a remarkable antitumor efficacy in a localized tumor model in mice.