Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models.

中文翻译：

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遗传稳定的脊髓灰质炎病毒载体可激活树突状细胞并引发抗肿瘤 CD8 T 细胞免疫。

病毒自然参与先天免疫，诱导抗原呈递，并介导 CD8 T 细胞启动以对抗外来抗原。脊髓灰质炎病毒可以为产生抗原特异性 CD8 T 细胞提供最佳环境，因为它们对树突状细胞具有天然趋向性，树突状细胞是 CD8 T 细胞免疫的卓越诱导剂；引发 Th1 促进炎症；并且不干扰先天或适应性免疫。然而，臭名昭著的遗传不稳定性和潜在的神经致病性阻碍了基于脊髓灰质炎病毒的载体应用。在这里，我们设计了一种基于脊髓灰质炎：鼻病毒嵌合体 PVSRIPO 的策略，在人类受试者脑内接种后没有病毒神经致病性，用于稳定表达外源抗原。PVSRIPO 载体在体外感染、激活和诱导 DC 中的表位呈递；它们在体内注射部位募集并激活具有 Th1 主导细胞因子特征的 DC。它们在体内有效引发肿瘤抗原特异性 CD8 T 细胞，诱导 CD8 T 细胞迁移至肿瘤部位，延缓肿瘤生长并提高小鼠肿瘤模型的存活率。