Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia
Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia
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DOI：
10.1038/mt.2013.154
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发表时间：
2013-11-01
影响因子：
12.4
通讯作者：
Prince, H. Miles
中科院分区：
文献类型：
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作者：
Ritchie, David S.;Neeson, Paul J.;Prince, H. Miles
在一项自体嵌合抗原受体（CAR）抗LeY T细胞治疗急性髓性白血病（AML）的I期研究中，我们检查了过继转移T细胞的安全性和输注后持久性。在含氟达拉滨的预处理后，4名患者接受了高达1.3 × 109个总T细胞，其中14-38%表达CAR。未观察到3级或4级毒性。一名患者实现了细胞遗传学缓解，而另一名活动性白血病患者外周血（PB）原始细胞减少，第三名患者表现出长期缓解。使用In 111标记的CAR T细胞的等分试样，我们证明了在具有最大临床益处的那些患者中向骨髓（BM）的运输。此外，在皮肤白血病患者中，CAR T细胞浸润了已证实的疾病部位。针对LeY转基因的PB和BM的系列PCR证明输注的CAR T细胞持续长达10个月。我们的研究支持CAR-T细胞疗法在高风险AML中的可行性和安全性，并证明了持久的体内持久性。
In a phase I study of autologous chimeric antigen receptor (CAR) anti-LeY T-cell therapy of acute myeloid leukemia (AML), we examined the safety and postinfusion persistence of adoptively transferred T cells. Following fludarabine-containing preconditioning, four patients received up to 1.3 x 109 total T cells, of which 14-38% expressed the CAR. Grade 3 or 4 toxicity was not observed. One patient achieved a cytogenetic remission whereas another with active leukemia had a reduction in peripheral blood (PB) blasts and a third showed a protracted remission. Using an aliquot of In 111-labeled CAR T cells, we demonstrated trafficking to the bone marrow (BM) in those patients with the greatest clinical benefit. Furthermore, in a patient with leukemia cutis, CAR T cells infiltrated proven sites of disease. Serial PCR of PB and BM for the LeY transgene demonstrated that infused CAR T cells persisted for up to 10 months. Our study supports the feasibility and safety of CAR-T-cell therapy in high-risk AML, and demonstrates durable in vivo persistence.