Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo
{"title":"腹膜定向嵌合溶瘤病毒CF17预防恶性腹水并提高癌症腹膜转移的存活率。","authors":"Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo","doi":"10.1016/j.omto.2023.100734","DOIUrl":null,"url":null,"abstract":"<p><p>Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines <i>in vitro</i> and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner <i>in vitro</i>. <i>In vivo</i>, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616379/pdf/","citationCount":"0","resultStr":"{\"title\":\"Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases.\",\"authors\":\"Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo\",\"doi\":\"10.1016/j.omto.2023.100734\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines <i>in vitro</i> and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner <i>in vitro</i>. <i>In vivo</i>, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.</p>\",\"PeriodicalId\":18869,\"journal\":{\"name\":\"Molecular Therapy Oncolytics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2023-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616379/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy Oncolytics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.omto.2023.100734\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/19 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy Oncolytics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omto.2023.100734","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/19 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases.
Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines in vitro and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner in vitro. In vivo, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.
期刊介绍:
Molecular Therapy — Oncolytics is an international, online-only, open access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer.