Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner. In mice bearing bilateral tumors in which only one is intratumorally injected, contralateral therapeutic effects are observed consistent with more prominent CD8 T-cell infiltrates and a treatment-related reduction of Tregs. Additive efficacy effects were observed upon co-treatment with intratumoral 17D and systemic anti-CD137 and anti-PD-1 immunostimulatory monoclonal antibodies. Importantly, when mice were preimmunized with 17D, intratumoral 17D treatment achieved better local and distant antitumor immunity. Such beneficial effects of prevaccination are in part explained by the potentiation of CD4 and CD8 T-cell infiltration in the treated tumor. The repurposed use of a GMP-grade vaccine to be given via the intratumoral route in prevaccinated patients constitutes a clinically feasible and safe immunotherapy approach.

中文翻译：

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重新使用黄热病疫苗进行肿瘤内免疫治疗。

Live 17D被广泛用作黄热病病毒的预防性疫苗株，可诱导针对野生型病原体的强力中和体液和细胞免疫。17D复制并杀死小鼠和人类肿瘤细胞系，但不会杀死未转化的人类细胞。肿瘤内注射有活性的17D可以显着延迟CD8 T细胞依赖性方式的移植肿瘤进程。在携带双侧肿瘤的小鼠中，仅向肿瘤内注射一种，观察到对侧治疗效果，与更显着的CD8 T细胞浸润和治疗相关的Treg降低相一致。在与肿瘤内17D和全身性抗CD137和抗PD-1免疫刺激性单克隆抗体共同治疗时，观察到了附加的功效效果。重要的是，当小鼠用17D预先免疫后，肿瘤内17D治疗获得了更好的局部和远距离抗肿瘤免疫力。预疫苗的这种有益作用部分地通过治疗的肿瘤中CD4和CD8 T细胞浸润的增强来解释。在预接种的患者中通过瘤内途径给予GMP级疫苗的重新用途构成了临床上可行且安全的免疫治疗方法。