文章：

T细胞衔接器在急性髓系白血病中的应用：分子靶点、结构及治疗挑战

T-Cell Engagers in Acute Myeloid Leukemia: Molecular Targets, Structure, and Therapeutic Challenges

原文发布日期：7 October 2025

DOI: 10.3390/cancers17193246

类型: Article

开放获取: 是

英文摘要：

The treatment of acute myeloid leukemia (AML) remains challenging, largely due to high relapse rates following standard therapies. T-cell engagers (TCEs) offer a promising immunotherapeutic approach by redirecting T cells to recognize and kill AML cells. These therapeutic proteins bind CD3 to T cells and a tumor-associated antigen to AML cells, facilitating targeted immune activation. While CD33 and CD123 are the most commonly targeted AML antigens, others such as CD135, CD38, and CLEC12A/CLL-1 are being evaluated in preclinical and clinical studies. In parallel, various TCE formats—including BiTEs, DuoBodies, DARTs, and DARPin-based constructs—have been developed to optimize pharmacokinetics, stability, and immune engagement. Despite the growing number of TCEs entering clinical evaluation, none have advanced beyond early Phase (I/II) trials, primarily due to the lack of optimal target antigens and challenges in balancing antileukemic activity with the risks of immune-related toxicities such as cytokine release syndrome (CRS). This review aims to summarize the current landscape of TCE development in AML, highlighting key targets, formats, and challenges.

摘要翻译： 

急性髓系白血病（AML）的治疗仍面临严峻挑战，这主要归因于标准疗法后的高复发率。T细胞衔接器（TCEs）作为一种前景广阔的免疫治疗策略，通过重定向T细胞识别并杀伤AML细胞发挥作用。这类治疗性蛋白能同时结合T细胞表面的CD3与AML细胞上的肿瘤相关抗原，从而启动靶向免疫激活。目前CD33和CD123是最常靶向的AML抗原，而CD135、CD38及CLEC12A/CLL-1等其他抗原也正处于临床前与临床研究评估阶段。与此同时，多种TCE结构形式——包括双特异性T细胞衔接器、双抗体、双亲和重靶向蛋白及锚蛋白重复蛋白结构等——已被开发用于优化药代动力学特性、稳定性和免疫激活效能。尽管进入临床评估的TCE数量日益增多，但尚无任何方案超越早期（I/II期）试验阶段，其主要原因在于缺乏理想靶点抗原，以及难以平衡抗白血病活性与免疫相关毒性（如细胞因子释放综合征）风险。本综述旨在系统阐述AML领域TCE研发现状，重点剖析关键靶点、结构形式及当前面临的挑战。

原文链接：

T-Cell Engagers in Acute Myeloid Leukemia: Molecular Targets, Structure, and Therapeutic Challenges