表达CD123嵌合抗原受体的T细胞用于治疗急性髓系白血病。
T cells expressing CD123 chimeric antigen receptors for treatment of acute myeloid leukemia.
作者信息
Mardiros Armen, Forman Stephen J, Budde Lihua E
机构信息
aKite Pharma, Inc., Santa Monica bDepartment of Hematology & Hematopoietic Cell Transplantation cDepartment of Cancer Immunotherapeutics dDepartment of Tumor Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
出版信息
Curr Opin Hematol. 2015 Nov;22(6):484-8. doi: 10.1097/MOH.0000000000000190.
Abstract
PURPOSE OF REVIEW
The purpose of this article is to discuss the rationale of targeting CD123 using chimeric antigen receptor (CAR) T cells for the treatment of leukemia.
RECENT FINDINGS
CD123 is a leukemia-associated antigen that expresses at high levels in leukemic stem cells and leukemic blasts and low level in normal hematopoietic stem/progenitor cells. Immune-based therapies targeting CD123 are being developed. Preclinical data suggest that CD123 CAR T cells exhibit potent antileukemic activity and various impacts on normal hematopoiesis.
SUMMARY
CD123 is an attractive surface target for novel antileukemic therapies. CD123 CAR T-cell-based immunotherapy is a promising treatment for patients with relapsed or refractory acute myeloid leukemia.
摘要
综述目的
本文旨在探讨使用嵌合抗原受体（CAR）T细胞靶向CD123治疗白血病的理论依据。
最新研究结果
CD123是一种白血病相关抗原，在白血病干细胞和白血病原始细胞中高表达，而在正常造血干/祖细胞中低表达。针对CD123的免疫疗法正在研发中。临床前数据表明，CD123 CAR T细胞具有强大的抗白血病活性，并对正常造血产生多种影响。
总结
CD123是新型抗白血病治疗的一个有吸引力的表面靶点。基于CD123 CAR T细胞的免疫疗法是复发或难治性急性髓系白血病患者的一种有前景的治疗方法。
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本文引用的文献
1
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Blood. 2016 Jan 7;127(1):122-31. doi: 10.1182/blood-2014-05-575704. Epub 2015 Nov 3.
2
Cancer statistics, 2015.
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5.
3
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.
Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13.
4
Chimeric antigen receptor T cells for sustained remissions in leukemia.
N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222.
5
A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia.
Leuk Lymphoma. 2015 May;56(5):1406-15. doi: 10.3109/10428194.2014.956316. Epub 2014 Nov 20.
6
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Mol Ther. 2015 Jan;23(1):184-91. doi: 10.1038/mt.2014.164. Epub 2014 Sep 1.
7
Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients.
Blood. 2014 Jul 17;124(3):385-92. doi: 10.1182/blood-2014-04-566737. Epub 2014 May 23.
8
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9
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