The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by theGraftvs.Leukemiaeffect occurring after allo-HSCT and in the context of donor leukocyte infusions. Various immunotherapeutic approaches, ranging from the use of antibodies, antibody–drug conjugates, bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cells, and therapeutic infusions of NK cells, are thus currently being tested with promising, yet conflicting, results. This review will concentrate on various types of immunotherapies in preclinical and clinical development, from the point of view of a clinical hematologist. The most promising therapies for clinical translation are the use of bispecific T-cell engagers and CAR-T cells aimed at lineage-restricted antigens, where overall responses (ORR) ranging from 20 to 40% can be achieved in a small series of heavily pretreated patients affected by refractory or relapsing leukemia. Toxicity consists mainly in the occurrence of cytokine-release syndrome, which is mostly manageable with step-up dosing, the early use of cytokine-blocking agents and corticosteroids, and myelosuppression. Various cytokine-enhanced natural killer products are also being tested, mainly as allogeneic off-the-shelf therapies, with a good tolerability profile and promising results (ORR: 20–37.5% in small trials). The in vivo activation of T lymphocytes and NK cells via the inhibition of their immune checkpoints also yielded interesting, yet limited, results (ORR: 33–59%) but with an increased risk of severe Graft vs. Host disease in transplanted patients. Therefore, there are still several hurdles to overcome before the widespread clinical use of these novel compounds.
免疫系统清除白血病细胞的潜力已在异基因造血干细胞移植后的移植物抗白血病效应及供体淋巴细胞输注中得到持续证实。目前，多种免疫治疗方法正在试验中，包括抗体、抗体-药物偶联物、双特异性T细胞衔接器、嵌合抗原受体T细胞以及自然杀伤细胞治疗性输注等，这些方法展现出前景广阔但结果不尽一致的疗效。本综述将从临床血液学家的视角，重点探讨临床前及临床研发阶段的各类免疫疗法。最具临床转化前景的治疗策略是针对谱系限制性抗原的双特异性T细胞衔接器和CAR-T细胞疗法，在难治性或复发性白血病的小样本重度预处理患者中可实现20%-40%的总体缓解率。其主要毒性反应包括细胞因子释放综合征（可通过阶梯式剂量递增、早期使用细胞因子阻断剂及皮质类固醇进行控制）以及骨髓抑制。多种细胞因子增强型自然杀伤细胞产品也正在试验中，主要作为通用型异体疗法，展现出良好的耐受性（小型试验中总体缓解率达20%-37.5%）。通过抑制免疫检查点在体内激活T淋巴细胞和自然杀伤细胞的方法虽取得一定疗效（总体缓解率33%-59%），但在移植患者中可能增加严重移植物抗宿主病的风险。因此，这些新型疗法在广泛临床应用前仍需克服诸多障碍。
The Immunotherapy of Acute Myeloid Leukemia: A Clinical Point of View
肿瘤(癌症)患者之家