Kathryn Ottolino-Perry, David Mealiea, Clara Sellers, Sergio A Acuna, Fernando A Angarita, Lili Okamoto, Deborah Scollard, Mihaela Ginj, Raymond Reilly, J Andrea McCart
{"title":"牛痘病毒与肽受体放射治疗协同提高腹膜癌的治疗效果。","authors":"Kathryn Ottolino-Perry, David Mealiea, Clara Sellers, Sergio A Acuna, Fernando A Angarita, Lili Okamoto, Deborah Scollard, Mihaela Ginj, Raymond Reilly, J Andrea McCart","doi":"10.1016/j.omto.2023.04.001","DOIUrl":null,"url":null,"abstract":"<p><p>Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and <sup>177</sup>Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of <sup>177</sup>Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. <sup>177</sup>Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"29 ","pages":"44-58"},"PeriodicalIF":5.3000,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/a9/main.PMC10173076.pdf","citationCount":"0","resultStr":"{\"title\":\"Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.\",\"authors\":\"Kathryn Ottolino-Perry, David Mealiea, Clara Sellers, Sergio A Acuna, Fernando A Angarita, Lili Okamoto, Deborah Scollard, Mihaela Ginj, Raymond Reilly, J Andrea McCart\",\"doi\":\"10.1016/j.omto.2023.04.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and <sup>177</sup>Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of <sup>177</sup>Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. <sup>177</sup>Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.</p>\",\"PeriodicalId\":18869,\"journal\":{\"name\":\"Molecular Therapy Oncolytics\",\"volume\":\"29 \",\"pages\":\"44-58\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2023-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/a9/main.PMC10173076.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy Oncolytics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.omto.2023.04.001\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"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.2023.04.001","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.
Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and 177Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of 177Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. 177Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.
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.