Tian Chen, Chen Zehui
Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Hotan District People's Hospital, Hotan, Xinjiang, China.
Blood Sci. 2022 Dec 15;5(1):15-24. doi: 10.1097/BS9.0000000000000140. eCollection 2023 Jan.
Although complete remission could be achieved in about 60%-70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates improved prognosis and reduced toxicities, which may offer novel therapeutic rationales. However, one of the major difficulties in developing immune therapies against AML is that the target antigens are also significantly expressed on healthy hematopoietic stem cells; B-cell malignancies are different because CD20/CD19/healthy B-cells are readily replaceable. Only the anti-CD33 antibody-drug conjugate gemtuzumab-ozogamicin is approved by the FDA for AML. Thus, drug development remains extremely active, although it is still in its infancy. This review summarizes the clinical results of immune therapeutic agents for AML, such as antibody-based drugs, chimeric antigen receptor therapy, checkpoint inhibitors, and vaccines.
尽管约60%-70%的急性髓系白血病(AML)患者在接受传统化疗后可实现完全缓解,但复发和治疗难治状态仍是主要死因。此外,对于所有身体虚弱的患者(包括因年龄/合并症以及与治疗相关的原因),非常需要强度较低的治疗方案。免疫疗法有望改善预后并降低毒性,这可能提供新的治疗理论依据。然而,开发针对AML的免疫疗法的主要困难之一是靶抗原在健康造血干细胞上也有显著表达;B细胞恶性肿瘤则不同,因为CD20/CD19/健康B细胞很容易被替代。只有抗CD33抗体药物偶联物吉妥珠单抗-奥唑米星被美国食品药品监督管理局(FDA)批准用于AML。因此,尽管药物研发仍处于起步阶段,但仍极为活跃。本综述总结了AML免疫治疗药物的临床结果,如基于抗体的药物、嵌合抗原受体疗法、检查点抑制剂和疫苗。