PDF(Pubmed)
Abstract：
The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by the Graft vs. Leukemia effect 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.
摘要：
移植物与移植物一致证明了免疫系统根除白血病细胞的潜力。allo-HSCT和供体白细胞输注后发生的白血病效应。各种免疫治疗方法，从抗体的使用，抗体-药物缀合物，双特异性T细胞衔接者，嵌合抗原受体（CAR）T细胞，和NK细胞的治疗性输注，因此，目前正在接受有希望的测试，但相互矛盾，结果。这篇综述将集中在临床前和临床发展中的各种类型的免疫疗法，从临床血液学家的角度来看。最有希望的临床翻译疗法是使用双特异性T细胞衔接剂和针对谱系限制性抗原的CAR-T细胞。其中，在一小部分严重预处理的难治性或复发性白血病患者中，总体缓解率（ORR）可达到20％至40％。毒性主要表现在细胞因子释放综合征的发生,通过逐步加药，这在很大程度上是可以控制的，早期使用细胞因子阻断剂和皮质类固醇，和骨髓抑制。各种细胞因子增强的自然杀伤产品也在测试中，主要作为同种异体现成的疗法，具有良好的耐受性和有希望的结果（ORR：小型试验中为20-37.5％）。T淋巴细胞和NK细胞通过抑制其免疫检查点的体内激活也产生了有趣的，但有限，结果（ORR：33-59％），但与严重移植的风险增加移植患者的宿主病。因此,在这些新化合物的广泛临床应用之前，仍有几个障碍需要克服。
