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利用T细胞靶向儿童急性髓系白血病:嵌合抗原受体、双特异性T细胞衔接器及其他。

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond.

作者信息

Epperly Rebecca, Gottschalk Stephen, Velasquez Mireya Paulina

机构信息

Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 77030, USA.

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 77030, USA.

出版信息

Children (Basel). 2020 Feb 17;7(2):14. doi: 10.3390/children7020014.

Abstract

Outcomes for pediatric patients with acute myeloid leukemia (AML) remain poor, highlighting the need for improved targeted therapies. Building on the success of CD19-directed immune therapy for acute lymphocytic leukemia (ALL), efforts are ongoing to develop similar strategies for AML. Identifying target antigens for AML is challenging because of the high expression overlap in hematopoietic cells and normal tissues. Despite this, CD123 and CD33 antigen targeted therapies, among others, have emerged as promising candidates. In this review we focus on AML-specific T cell engaging bispecific antibodies and chimeric antigen receptor (CAR) T cells. We review antigens being explored for T cell-based immunotherapy in AML, describe the landscape of clinical trials upcoming for bispecific antibodies and CAR T cells, and highlight strategies to overcome additional challenges facing translation of T cell-based immunotherapy for AML.

摘要

急性髓系白血病(AML)患儿的治疗效果仍然很差,这凸显了改进靶向治疗的必要性。基于针对急性淋巴细胞白血病(ALL)的CD19导向免疫疗法的成功经验,目前正在努力为AML开发类似的策略。由于造血细胞和正常组织中存在高表达重叠,因此识别AML的靶抗原具有挑战性。尽管如此,CD123和CD33抗原靶向疗法等已成为有前景的候选疗法。在本综述中,我们重点关注AML特异性T细胞衔接双特异性抗体和嵌合抗原受体(CAR)T细胞。我们回顾了正在探索用于AML基于T细胞免疫疗法的抗原,描述了双特异性抗体和CAR T细胞即将开展的临床试验情况,并强调了克服AML基于T细胞免疫疗法转化面临的其他挑战的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d982/7072334/03e0a0c6de10/children-07-00014-g001.jpg

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