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。

Frontiers in molecular medicine Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI:10.3389/fmmed.2024.1461151
Grace Haroun, Erlinda M Gordon
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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。
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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.

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