通用型碱基编辑 CAR7 T 细胞治疗 T 细胞急性淋巴细胞白血病
Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia
T 细胞急性淋巴细胞白血病复发或难治时预后很差，需要新疗法。研究者用碱基编辑技术敲除 T 细胞上的三个基因，制成不会互相攻击、可通用供应的抗 CD7 嵌合抗原受体（CAR）T 细胞，输注给 9 名儿童和 2 名成人患者。结果显示没有出现不可接受的不良事件，所有患者在第 28 天都达到完全缓解，其中 9 人（82%）达到深度缓解并成功接受异基因造血干细胞移植。随访 3 至 36 个月，11 人中 7 人（64%）仍处于持续缓解。这表明通用型碱基编辑 CAR T 细胞可作为移植前的桥接治疗。
为什么推荐给您：碱基编辑通用型 CAR T 细胞首次人体试验取得阳性结果，属全新治疗模态的里程碑。
不需要生物学背景，多打比方
正在获取全文并生成讲解（拿不到全文就依据摘要），大约需要 30–60 秒…
已等待 0 秒
这篇还没有动画
动画会把研究的流程、作用机制和关键结果一步一步演示出来，每一步都标明出自原文哪里。制作大约需要 30–60 秒。
摘要Abstract
BACKGROUND: CD7 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory T-cell acute lymphoblastic leukemia (ALL). Supportive results of first-in-human studies of base-edited anti-CD7 CAR (BE-CAR7) T cells with triple C→T deamination-mediated knockouts of TCRαβ, CD52, and CD7 have been reported previously.
METHODS: In a phase 1 study, we administered BE-CAR7 T cells to children (≤16 years of age) with relapsed or refractory T-cell ALL after they had undergone lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab. Adults with compassionate-use access arrangements were also eligible. Patients who had remission by day 28 after the BE-CAR7 T-cell infusion proceeded to allogeneic hematopoietic stem-cell transplantation. The primary outcome was safety. Secondary outcomes included duration of remission, disease-free survival, and overall survival.
RESULTS: BE-CAR7 T cells were administered to 9 children, as well as to 2 adults who were treated under compassionate-use access arrangements. Lymphodepletion and BE-CAR7 infusions did not lead to unacceptable adverse events, and circulating CAR7 T cells were detected in all the patients. Complications included cytokine release syndrome of grades 1 through 4, transient rashes, multilineage cytopenia, and opportunistic infections. All the patients had complete morphologic remission with incomplete count recovery at day 28. Nine patients (82%) had deep remission (according to flow cytometry or polymerase-chain-reaction assay) that allowed them to proceed to stem-cell transplantation, and 2 patients with quantifiable minimal residual disease in bone marrow received palliative care. Transplantation eliminated remaining BE-CAR7 T cells and supported donor-derived, multilineage reconstitution. Viral reactivations were frequent, and 3 patients had clinically significant virus-related complications after transplantation. Overall, 7 of the 11 patients (64%) who received the investigational therapy were in ongoing remission at 3 to 36 months after transplantation, and leukemia with loss of CD7 expression was documented in 2 patients.
CONCLUSIONS: Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients. (Funded by the Medical Research Council and others; ISRCTN Registry number, ISRCTN15323014.).