肿瘤细胞治疗研究
英文原题：CD123-targeting immunotherapeutic approaches in acute myeloid leukaemia.
复发性或难治性急性髓系白血病（AML）的治疗仍然是一项重大挑战，可用的靶向免疫疗法有限。
复发或难治性急性髓系白血病（AML）的治疗仍然是一项重大挑战，可用的靶向免疫疗法有限。CD123，即白细胞介素-3（IL-3）受体，长期以来被认为是表达于AML原始细胞上的潜在靶点，针对CD123的一系列不同方法已进入试验，观察到了不同的抗肿瘤反应和毒性。在此，我们综述了这些疗法的临床结局，包括单克隆抗体和抗体药物偶联物，以及双特异性T细胞衔接分子和嵌合抗原受体（CAR）T细胞。我们讨论了治疗相关毒性和疗效有限的潜在原因，包括抗原表达差异、AML微环境和患者来源T细胞适应性。为应对这些挑战，我们重点介绍了目前处于临床前开发阶段的CD123靶向新方法。有前景的新策略包括靶向CD123和其他已知AML相关抗原（如CD33或CLL-1）的联合疗法、基于NK细胞的细胞疗法以及双特异性分泌型T细胞。
Treatment of relapsed or refractory acute myeloid leukaemia (AML) has remained a significant challenge, with limited available targeted immunotherapies. CD123, or the interleukin-3 (IL-3) receptor, has long been known as a potential target expressed on AML blasts, and a range of different approaches to targeting CD123 have been trialled with variable anti-tumour responses and toxicities observed. Here, we review the clinical outcomes of these therapies, including monoclonal antibodies and antibody-drug conjugates, as well as bispecific T-cell engager molecules and chimeric antigen receptor (CAR) T cells. We discuss the potential reasons for therapy-associated toxicity and limited efficacy, including differential antigen expression, the AML microenvironment and patient-derived T-cell fitness. To address these challenges, we highlight novel approaches to CD123 targeting currently in preclinical development. Promising new strategies include combination therapies that target CD123 and other known AML-associated antigens such as CD33 or CLL-1, NK-cell-based cell therapies, and bispecific-secreting T cells.
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