肿瘤细胞治疗研究
英文原题：Efficacy and safety of autologous CD5-KO anti-CD5 CAR-T cells in relapsed/refractory CD5(+) hematological malignancies.
这些发现证明了 CT125A 在 CD5⁺ 恶性肿瘤中的治疗潜力，同时凸显了安全性优化的必要性。
靶向正常T细胞共有抗原的嵌合抗原受体（CAR）T细胞治疗，需要进行基因改造以避免自相残杀。本项1期试验在7例复发/难治性CD5阳性血液系统恶性肿瘤患者中评估自体CD5靶向CAR-T细胞CT125A（敲除CD5基因）的疗效和安全性。总体缓解率为85.7%，其中4例完全缓解。所有患者均发生细胞因子释放综合征（6例1–2级，1例3级），2例出现免疫效应细胞相关神经毒性综合征。最常见的3级不良事件为血细胞减少和感染，另观察到皮疹及自身免疫相关事件等特征性表现。输注后免疫表型分析显示，CD5阳性T细胞和CD19阳性B细胞持续减少，CD4/CD8比值降低。人CD5敲入小鼠模型出现皮肤病变，但重要器官未见显著受累。结果显示CT125A对CD5阳性恶性肿瘤具有治疗潜力，同时提示仍需优化安全性。试验注册号：ClinicalTrials.gov NCT04767308。
Chimeric antigen receptor (CAR)-T cell therapy targeting antigens shared with normal T cells requires genetic modifications to prevent fratricide. This phase 1 trial evaluates autologous CD5-targeting CAR-T cells with CD5 gene deletion (CT125A) in seven patients with relapsed/refractory CD5 + hematologic malignancies. The overall response rate is 85.7%, including four complete responses. All patients experience cytokine release syndrome (six grade 1-2, one grade 3), and two patients develop immune effector cell-associated neurotoxicity syndrome. The most common grade 3 adverse events are cytopenia and infection, with unique observations of rash and autoimmune-related events. Post-infusion immunophenotyping shows persistent depletion of CD5 + T cells and CD19 + B cells, with reduced CD4/CD8 ratios. The human CD5 knockin murine model reveals skin lesions without significant vital organ involvement. These findings demonstrate CT125A's therapeutic potential in CD5 + malignancies while highlighting the need for safety optimization. The trial has been registered at ClinicalTrials.gov (NCT04767308).
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