Centre for Haematology, Department of Immunology and Inflammation, Imperial College of Science, Technology and Medicine, London, SW7 2BX, UK.
Curr Treat Options Oncol. 2023 May;24(5):381-386. doi: 10.1007/s11864-023-01066-3. Epub 2023 Mar 22.
Although safe and effective immune therapies have been developed in several cancers, this has not been so in acute myeloid leukaemia (AML). Studies of antibodies to CD33, CD123 and CLL-1 report with unconvincing efficacy and substantial adverse events. Lacking AML-specific target antigens, these approaches using non-specific antigen targets often cause unacceptable bone marrow toxicity and off-target adverse events. Studies of AML incidence in persons with immune deficiency indicate little if any immune surveillance against AML. In contrast, data studies of recipients of haematopoietic cell transplants support an effective allogeneic anti-AML effect associated with graft-versus-host disease (GvHD) and possibly a specific graft-versus-leukaemia (GvL) effect. A special problem in the immune therapy of AML is few neo-antigens compared with solid cancers because of a relatively low mutation frequency. Studies of CAR-T-, CAR-NK-adaptor CAR-T- and allogeneic NK-cells are progressing as are approaches using synthetic biology. Presently, there are no convincing data of efficacy of immune therapy in AML.
尽管在几种癌症中已经开发出安全有效的免疫疗法，但急性髓细胞白血病（AML）并非如此。针对 CD33、CD123 和 CLL-1 的抗体的研究报告显示其疗效并不令人信服，且有大量不良反应。由于缺乏 AML 特异性靶抗原，这些使用非特异性抗原靶标的方法通常会导致不可接受的骨髓毒性和脱靶不良反应。免疫缺陷者中 AML 发病率的研究表明，针对 AML 的免疫监视很少（如果有的话）。相比之下，造血细胞移植受者的数据研究支持与移植物抗宿主病（GvHD）相关的有效的同种异体抗 AML 作用，并且可能具有特定的移植物抗白血病（GvL）作用。AML 的免疫治疗中的一个特殊问题是与实体瘤相比，新抗原较少，因为其突变频率相对较低。嵌合抗原受体-T 细胞（CAR-T）、嵌合抗原受体自然杀伤细胞（CAR-NK）-适配器 CAR-T 和同种异体 NK 细胞的研究正在进展中，同时也在使用合成生物学方法。目前，AML 免疫治疗的疗效尚无令人信服的数据。
