{"title":"DeltaRex-G,编码 CCNG1 抑制剂的肿瘤靶向逆向载体,用于治疗 CAR-T 细胞疗法诱导的细胞因子释放综合征。","authors":"Grace Haroun, Erlinda M Gordon","doi":"10.3389/fmmed.2024.1461151","DOIUrl":null,"url":null,"abstract":"<p><p>Cytokine release syndrome is a serious complication of chimeric antigen receptor-T cell therapy and is triggered by excessive secretion of inflammatory cytokines by chimeric T cells which could be fatal. Following an inquiry into the molecular mechanisms orchestrating cytokine release syndrome, we hypothesize that DeltaRex-G, a tumor targeted retrovector encoding a cytocidal CCNG1 inhibitor gene, may be a viable treatment option for corticosteroid-resistant cytokine release syndrome. DeltaRex-G received United States Food and Drug Administration Emergency Use Authorization to treat Covid-19-induced acute respiratory distress syndrome, which is due to hyperactivated immune cells. A brief administration of DeltaRex-G would inhibit a certain proportion of hyperactive chimeric T cells, consequently reducing cytokine release while retaining chimeric T cell efficacy.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1461151"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445129/pdf/","citationCount":"0","resultStr":"{\"title\":\"DeltaRex-G, tumor targeted retrovector encoding a CCNG1 inhibitor, for CAR-T cell therapy induced cytokine release syndrome.\",\"authors\":\"Grace Haroun, Erlinda M Gordon\",\"doi\":\"10.3389/fmmed.2024.1461151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cytokine release syndrome is a serious complication of chimeric antigen receptor-T cell therapy and is triggered by excessive secretion of inflammatory cytokines by chimeric T cells which could be fatal. Following an inquiry into the molecular mechanisms orchestrating cytokine release syndrome, we hypothesize that DeltaRex-G, a tumor targeted retrovector encoding a cytocidal CCNG1 inhibitor gene, may be a viable treatment option for corticosteroid-resistant cytokine release syndrome. DeltaRex-G received United States Food and Drug Administration Emergency Use Authorization to treat Covid-19-induced acute respiratory distress syndrome, which is due to hyperactivated immune cells. A brief administration of DeltaRex-G would inhibit a certain proportion of hyperactive chimeric T cells, consequently reducing cytokine release while retaining chimeric T cell efficacy.</p>\",\"PeriodicalId\":73090,\"journal\":{\"name\":\"Frontiers in molecular medicine\",\"volume\":\"4 \",\"pages\":\"1461151\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445129/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in molecular medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/fmmed.2024.1461151\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in molecular medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fmmed.2024.1461151","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
细胞因子释放综合征是嵌合抗原受体-T 细胞疗法的一种严重并发症,由嵌合 T 细胞过度分泌炎症细胞因子引发,可能致命。在对细胞因子释放综合征的分子机制进行研究后,我们假设,DeltaRex-G(一种编码细胞杀伤性 CCNG1 抑制剂基因的肿瘤靶向逆转录载体)可能是治疗皮质类固醇耐药细胞因子释放综合征的一种可行方法。DeltaRex-G 获得了美国食品和药物管理局的紧急使用授权,可用于治疗 Covid-19 引发的急性呼吸窘迫综合征,这种综合征是由过度激活的免疫细胞引起的。短暂服用 DeltaRex-G 可抑制一定比例的高活性嵌合 T 细胞,从而减少细胞因子的释放,同时保持嵌合 T 细胞的功效。
DeltaRex-G, tumor targeted retrovector encoding a CCNG1 inhibitor, for CAR-T cell therapy induced cytokine release syndrome.
Cytokine release syndrome is a serious complication of chimeric antigen receptor-T cell therapy and is triggered by excessive secretion of inflammatory cytokines by chimeric T cells which could be fatal. Following an inquiry into the molecular mechanisms orchestrating cytokine release syndrome, we hypothesize that DeltaRex-G, a tumor targeted retrovector encoding a cytocidal CCNG1 inhibitor gene, may be a viable treatment option for corticosteroid-resistant cytokine release syndrome. DeltaRex-G received United States Food and Drug Administration Emergency Use Authorization to treat Covid-19-induced acute respiratory distress syndrome, which is due to hyperactivated immune cells. A brief administration of DeltaRex-G would inhibit a certain proportion of hyperactive chimeric T cells, consequently reducing cytokine release while retaining chimeric T cell efficacy.