Neoadjuvant use of oncolytic herpes virus G47D prevents local recurrence after insufficient resection in tongue cancer models

A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47A (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47A exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47A signifi- cantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47A (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47A and resection led to 10/10 survival (120 days), whereas the survivals for G47A alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47A therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47A therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47A is useful for preventing local recurrence after tongue cancer surgery.