Haroun Grace, Gordon Erlinda M
University of California, Los Angeles, Los Angeles, CA, United States.
Sarcoma Oncology Research Center, Santa Monica CA, Aveni Foundation, Santa Monica, CA, United States.
Front Mol Med. 2024 Sep 18;4:1461151. doi: 10.3389/fmmed.2024.1461151. eCollection 2024.
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.
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细胞过度分泌炎性细胞因子引发，可能致命。在探究调控细胞因子释放综合征的分子机制后，我们推测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，可能是治疗对皮质类固醇耐药的细胞因子释放综合征的可行选择。DeltaRex-G已获得美国食品药品监督管理局的紧急使用授权，用于治疗由免疫细胞过度激活引起的新冠病毒诱导的急性呼吸窘迫综合征。短暂给予DeltaRex-G会抑制一定比例的过度活跃的嵌合T细胞，从而减少细胞因子的释放，同时保留嵌合T细胞的疗效。
