Inoue Kosuke, Ito Hirotaka, Iwai Miwako, Tanaka Minoru, Mori Yoshiyuki, Todo Tomoki
Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Department of Oral and Maxillofacial Surgery, Jichi Medical University Hospital, Tochigi 329-0498, Japan.
Mol Ther Oncolytics. 2023 Jul 19;30:72-85. doi: 10.1016/j.omto.2023.07.002. eCollection 2023 Sep 21.
A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ 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 G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ 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 G47Δ 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. G47Δ 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 G47Δ is useful for preventing local recurrence after tongue cancer surgery.
舌癌的完整切除往往很困难。我们研究了在切除术前给予G47Δ（teserpaturev，一种三重突变的1型溶瘤单纯疱疹病毒）的有效性。G47Δ在所有测试的头颈癌细胞系中均表现出良好的细胞病变效应和复制能力。在C3H/He小鼠的原位SCCVII舌癌模型中，瘤内接种G47Δ可显著延长生存期。此外，患有原位舌癌的小鼠接受了新辅助G47Δ（或模拟物）治疗，并进行或不进行“半侧”切除，最大程度地避免了手术死亡。新辅助G47Δ和切除导致10/10存活（120天），而单独使用G47Δ和单独切除的存活率分别为6/10和5/10：所有对照动物在第11天死亡。此外，即使将切除区域缩小至“部分”，即提供不足的切除边缘，新辅助G47Δ治疗仍可实现100%存活，而单独的半侧切除导致一半动物因局部复发而死亡。G47Δ治疗导致肿瘤浸润的CD8和CD4细胞数量增加，残留舌内的F4/80细胞增加，以及肿瘤内和肿瘤周围免疫相关基因的表达增加。这些结果表明，新辅助使用G47Δ有助于预防舌癌手术后的局部复发。
