CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia
CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia
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DOI：
10.1016/j.ymthe.2018.10.001
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发表时间：
2019-01-02
影响因子：
12.4
通讯作者：
Mamonkin, Maksim
中科院分区：
文献类型：
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作者：
Gomes-Silva, Diogo;Atilla, Erden;Mamonkin, Maksim
嵌合抗原受体（CAR） T细胞治疗急性髓系白血病（AML）有对正常髓系细胞产生毒性的风险。CD7在大约30%的AML患者的白血病母细胞和恶性祖细胞中表达，但在正常的髓细胞和红细胞中不表达。由于恶性细胞的CD7表达也与化疗耐药和不良预后有关，靶向这种抗原可能对这部分AML患者有益。在这里，我们发现在CD7基因编辑（CD7(KO)） T细胞中表达CD7导向的CAR可以有效地消除CD7(+) AML细胞系、原发CD7(+) AML和集落形成细胞，但保留髓系和红系祖细胞及其后代。在异种移植模型中，CD7 CAR - T细胞保护小鼠免受系统性白血病的侵袭，延长了生存期。我们的研究结果支持使用CD7(KO) CD7 CAR - T细胞治疗CD7(+) AML的非清髓性治疗的可行性。
Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7(KO)) T cells effectively eliminates CD7(+) AML cell lines, primary CD7(+) AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7(KO) CD7 CAR T cells for the non-myeloablative treatment of CD7(+) AML.