肿瘤细胞治疗研究
英文原题：First-in-human study of FLT3 CAR-T cell therapy for relapsed acute myeloid leukemia.
在这项首次人体开放标签研究中，自体 FLT3 CAR-T 细胞被输注给 2 例复发/难治性 FLT3⁺ 急性髓系白血病患者。
在这项首次人体、开放标签研究中，研究者将自体 FLT3 CAR-T 细胞用于 2 名复发和难治性 FLT3 阳性 AML 患者。骨髓检查显示 AML 原始细胞表面 FLT3 高表达，但表达水平存在差异。肿瘤减负和淋巴细胞清除后，患者接受 1×10⁶ 个细胞/kg 的 FLT3 CAR-T，随后两人均出现 CAR-T 细胞体内扩增和 1 级细胞因子释放综合征。两名患者均未能在 CAR-T 治疗后达到缓解；但治疗后的骨髓检查显示 FLT3 阳性 AML 原始细胞被清除，而 FLT3 阴性 AML 原始细胞仍存在，且治疗早期正常 CD34⁺造血干/祖细胞（HSPC）得到保留，这些细胞的 FLT3 表达水平不一。总体而言，自体 FLT3 CAR-T 可安全给药，并能以较低毒性清除 FLT3 阳性原始细胞，而不会对正常 CD34⁺ HSPC 造成明显损害；但由于 FLT3 表达异质性及 FLT3 阴性 AML 原始细胞持续存在，未能诱导白血病缓解。
In this first-in-human open-label study, autologous FLT3 CAR-T cells were delivered to two patients with relapsed and refractory FLT3 + AML. Bone marrow examination revealed AML blasts with high but variable surface density of FLT3 expression. Following tumor cytoreduction and lymphodepletion, 1 10 6 /kg of FLT3 CAR-T cells were administered, resulting in in vivo CAR-T cell expansion and grade 1 cytokine release syndrome in both patients. Both patients failed to achieve remission after CAR-T cell therapy, but bone marrow examination following therapy revealed the elimination of FLT3 + AML blasts, persistence of FLT3 - AML blasts, and early post-treatment preservation of normal CD34 + hematopoietic stem and progenitor cells (HSPCs) with variable FLT3 expression. Collectively, autologous FLT3 CAR-T cells can be safely administered and can eradicate FLT3 blasts with minimal toxicity, without causing substantial damage to normal CD34 HSPCs; however, they fail to induce leukemic remission due to the heterogeneity of FLT3 expression and the persistence of FLT3 AML blasts.
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