G47Δ病毒在舌癌模型中的新辅助治疗应用可以预防不完全切除后的局部复发。
Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.
发表日期:2023 Sep 21
作者:
Kosuke Inoue, Hirotaka Ito, Miwako Iwai, Minoru Tanaka, Yoshiyuki Mori, Tomoki Todo
来源:
Cell Death & Disease
摘要:
舌癌的完全切除通常很困难。我们研究了在切除手术之前给予G47Δ(teserpaturev),一种三次突变的溶瘤性单纯疱疹病毒1型,的应用的可行性。在测试的所有头颈癌细胞系中,G47Δ表现出良好的细胞病理效应和复制能力。在C3H/He小鼠的正位SCCVII舌癌模型中,G47Δ作用下的肿瘤内接种显著延长了生存期。此外,具有正位舌癌的小鼠接受新辅助G47Δ(或模拟)疗法,有无"半侧"切除(最大限度地避免外科死亡)。新辅助G47Δ和切除导致10/10的生存(120天),而G47Δ单独和切除单独的生存分别为6/10和5/10:所有对照动物在第11天前死亡。此外,即使切除范围缩小为"部分",导致切除范围不足,新辅助G47Δ疗法也实现了100%的生存,而半侧切除单独导致了一半动物的局部复发致死。G47Δ疗法导致了肿瘤浸润的CD8+和CD4+细胞数量增加,残留舌部的F4/80+细胞增加,并在肿瘤内外表达免疫相关基因。这些结果表明,在舌癌手术后预防局部复发方面,新辅助使用G47Δ是有用的。© 2023 作者
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.© 2023 The Author(s).