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Oral reovirus produces no gross toxicities, suppresses multifocal tumor lesions, and acts through Peyer’s patches in the terminal ileum by increasing IgA+ antibody-secreting cells via MAdCAM-1+ blood vessels and reshaping the gut microbiome. It promotes antigen presentation, type I/II interferons, and T cell activation in distant tumors without direct infection beyond the gastrointestinal tract, requiring gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells for effective antitumor immunity.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/oral-reovirus-reshapes-the-gut-microbiome-and-enhances-antitumor-immunity-in-colon-cancer-received-19-september-2023/331447/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/oral-reovirus-reshapes-the-gut-microbiome-and-enhances-antitumor-immunity-in-colon-cancer-received-19-september-2023/331447.png","ImageObject",300,407,{"name":92,"@type":93},"Sage","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the purpose of using orally administered RC402 in colon cancer?","Question",{"text":112,"@type":113},"To induce antitumor immunity through oral oncolytic virotherapy. The study examines whether oral reovirus can suppress tumors and activate immune responses beyond the gastrointestinal tract.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Does oral reovirus directly infect tumor cells outside the gut?",{"text":117,"@type":113},"No. The study states that oral reovirus does not reach or directly infect tumor cells beyond the gastrointestinal tract, yet still promotes immune activation in distant tumors.",{"name":119,"@type":110,"acceptedAnswer":120},"What factors are required for orally administered reovirus to generate antitumor immunity?",{"text":121,"@type":113},"The presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are described as indispensable for the observed antitumor immunity.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331447,1790816768,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},687197207057,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article [https://doi.org/10.1038/s41467-024-53347-6](https://doi.org/10.1038/s41467-024-53347-6)  \nOral reovirus reshapes the gut microbiome and enhances antitumor immunity in colon cancer  \nReceived: 19 September 2023  \n\n| Accepted: 2 October 2024 |\n| --- |\n| |\n| Check for updates |\n\nWon Suk Lee 1,2,6, Seung Joon Lee1,2,6, Hye Jin Lee1,2,6, Hannah Yang 1,2, Eun-Jin Go1,2, Enkhtaivan Gansukh3, Ki-Hoon Song3, Xiao Xiang4,  \nDong Guk Park 3,5, Tommy Alain4, Hong Jae Chon 1,2  & Chan Kim 1,2   \nThe route ofoncolytic virotherapy is pivotal for immunotherapeutic efficacy in advanced cancers. In this preclinical study, an oncolytic reovirus (RC402) isorally 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.  \nOncolytic viruses (OVs) are therapeutic agents that have been selected or genetically engineered to specifically infect and lyse tumor cells without affecting normal cells1–5. The tumor selectivity of OVs is owing to the parallel interplay of oncogenic mechanisms and viral signaling, which renders cancer cells vulnerable to viral infection6,7. Cancer cells evade immune surveillance by suppressing interferon (IFN) signaling and IFN is a critical component of antiviral defense. Therefore, cancer cells have intrinsic vulnerability to viral infection8,9. Moreover, dysregulation of RAS, TP53, and RB signaling pathways in cancer cells increases their susceptibility to viral infection10,11.  \nReoviruses area class of OVs that cause self-limited asymptomatic or mild infections of the upper respiratory and gastrointestinal (GI) tracts in humans12–14. They are non-enveloped viruses with 10 doublestranded RNA segments encoding proteins that allow them to evade antiviral IFN responses15,16. Reovirus σ1binds with high affinity toJAM-1, which is overexpressed on the surface of various cancer cells, resulting in receptor-mediated endocytosis of reovirus17. Moreover, reoviruses preferentially replicate in transformed tumor cells compared with normal cells because of the suppressed antiviral defense, increased proteolytic activity, and dysregulated protein synthesis often present in cancer cells18,19. Reoviruses induce tumor cell oncolysis by triggering  \n1Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. 2Laboratory of Translational Immuno-Oncology, CHA University, Seongnam, Gyeonggi-do, Republic of Korea. 3Virocure Inc., Seoul, Republic of Korea. 4Department of Biochemistry, Microbiology, and Immunology, Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada. 5Department of Surgery, School of Medicine, Dankook University, Cheonan, Republic of Korea. 6These authors contributed equally: Won Suk Lee,  \nSeung Joon Lee, Hye Jin Lee. [e-mail:](e-mail: minidoctor@cha.ac.kr)[ minidoctor@cha.ac.kr](e-mail: minidoctor@cha.ac.kr); [chan@cha.ac.kr](chan@cha.ac.kr); [larrel80@gmail.com](larrel80@gmail.com)  \nvario","cbCaic6mC1jzn15p","https://ap.wps.com/l/cbCaic6mC1jzn15p","pdf",5265343,15,"English","# Abstract\n## Oral RC402 antitumor effects and safety\n## Mechanistic role of gut immunity and microbiome\n## Comparison with intratumoral administration\n## Synergy with checkpoint blockade","[{\"question\":\"What is the purpose of using orally administered RC402 in colon cancer?\",\"answer\":\"To induce antitumor immunity through oral oncolytic virotherapy. The study examines whether oral reovirus can suppress tumors and activate immune responses beyond the gastrointestinal tract.\"},{\"question\":\"Does oral reovirus directly infect tumor cells outside the gut?\",\"answer\":\"No. The study states that oral reovirus does not reach or directly infect tumor cells beyond the gastrointestinal tract, yet still promotes immune activation in distant tumors.\"},{\"question\":\"What factors are required for orally administered reovirus to generate antitumor immunity?\",\"answer\":\"The presence of the gut microbiome, Batf3+ dendritic cells, type I interferons, and CD8+ T cells are described as indispensable for the observed antitumor immunity.\"}]","Oral reovirus reshapes the gut microbiome and enhances antitumor immunity in colon cancer - Received 19 September 2023 | PDF",1789993288,38]