Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.
Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea.
Nat Commun. 2024 Oct 22;15(1):9092. doi: 10.1038/s41467-024-53347-6.
The route of oncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) is orally administered to induce antitumor immunity. Oral reovirus treatment shows no gross toxicities and effectively suppresses multifocal tumor lesions. Orally administered reovirus interacts with the host immune system in the Peyer's patch of the terminal ileum, increases IgA antibody-secreting cells in the lamina propria through MAdCAM-1 blood vessels, and reshapes the gut microbiome. Oral reovirus promotes antigen presentation, type I/II interferons, and T cell activation within distant tumors, but does not reach or directly infect tumor cells beyond the gastrointestinal tract. In contrast to intratumoral reovirus injection, the presence of the gut microbiome, Batf3 dendritic cells, type I interferons, and CD8 T cells are indispensable for orally administered reovirus-induced antitumor immunity. Oral reovirus treatment is most effective when combined with αPD-1(L1) and/or αCTLA-4, leading to complete colon tumor regression and protective immune memory. Collectively, oral reovirus virotherapy is a feasible and effective immunotherapeutic strategy in preclinical studies.
溶瘤病毒治疗的途径对于晚期癌症的免疫治疗效果至关重要。在这项临床前研究中，我们采用口服方式给予溶瘤呼肠孤病毒（RC402）以诱导抗肿瘤免疫。口服溶瘤病毒治疗没有明显的毒性作用，并能有效抑制多灶性肿瘤病变。口服病毒在回肠末端的派尔集合淋巴结与宿主免疫系统相互作用，通过 MAdCAM-1 血管增加固有层中的 IgA 抗体分泌细胞，并重塑肠道微生物组。口服溶瘤病毒在远处肿瘤内促进抗原呈递、I 型/II 型干扰素和 T 细胞激活，但不会到达或直接感染胃肠道以外的肿瘤细胞。与瘤内注射相比，肠道微生物组、Batf3 树突状细胞、I 型干扰素和 CD8 T 细胞的存在对于口服溶瘤病毒诱导的抗肿瘤免疫是必不可少的。口服溶瘤病毒治疗与 αPD-1（L1）和/或 αCTLA-4 联合使用效果最佳，可导致完全结肠肿瘤消退和保护性免疫记忆。总的来说，口服溶瘤病毒治疗是一种可行且有效的临床前免疫治疗策略。
