Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.
Department of Medicine, Section of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Blood Rev. 2019 Mar;34:67-83. doi: 10.1016/j.blre.2018.12.001. Epub 2018 Dec 5.
Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development. Here, we review recent advances in antibody-based therapy, immune checkpoint inhibitors, vaccines and adoptive cell-based therapy for patients with AML and MDS. First, we discuss different antibody constructs. Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1) and CD47 as well as peptide, dendritic cell and dendritic/AML cell-based vaccines are reviewed next. Lastly, adoptive cell-based therapy including chimeric antigen receptor (CAR)-T cell and NK cell therapy is discussed.
免疫疗法已经彻底改变了实体瘤和液体恶性肿瘤的治疗方法。异体造血干细胞移植（HSCT）能够治愈急性髓系白血病（AML）和骨髓增生异常综合征（MDS），这证明了免疫疗法在 AML 和 MDS 中的应用具有概念验证意义。然而，除了 HSCT 之外，目前只有抗 CD33 抗体药物偶联物吉妥珠单抗奥佐米星被批准为 AML 的抗体靶向治疗药物。目前，多种免疫治疗药物正在不同的临床开发阶段。在这里，我们回顾了针对 AML 和 MDS 患者的基于抗体的治疗、免疫检查点抑制剂、疫苗和过继细胞治疗的最新进展。首先，我们讨论了不同的抗体结构。接下来，我们回顾了靶向细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）、程序性细胞死亡蛋白 1（PD-1）和 CD47 的免疫检查点抑制剂、肽、树突状细胞和树突状/AML 细胞疫苗。最后，我们讨论了过继细胞治疗，包括嵌合抗原受体（CAR）-T 细胞和 NK 细胞治疗。
