Amberger Daniel Christoph, Schmetzer Helga Maria
Department of Medicine III, University Hospital, Hematopoetic Cell Transplantation, Munich, Germany.
Transfus Med Hemother. 2020 Dec;47(6):432-443. doi: 10.1159/000512452. Epub 2020 Nov 5.
The prognosis of elderly patients with acute myeloid leukemia (AML) and high-grade myelodysplastic syndrome (MDS) is limited due to the lack of therapy options and high relapse rates. Dendritic cell (DC)-based immunotherapy seems to be a promising treatment tool. DC are potent antigen-presenting cells and play a pivotal role on the interface of the innate and the adaptive immune system. Myeloid leukemia blasts can be converted to DC of leukemic origin (DC), expressing costimulatory molecules along with the whole leukemic antigen repertoire of individual patients. These generated DC are potent stimulators of various immune reactive cells and increase antileukemic immunity ex vivo. Here we review the generating process of DC/DC from leukemic peripheral blood mononuclear cells as well as directly from leukemic whole blood with "minimized" Kits to simulate physiological conditions ex vivo. The purpose of adoptive cell transfer of DC/DC as a vaccination strategy is discussed. A new potential therapy option with Kits for patients with myeloid leukemia, which would render an adoptive DC/DC transfer unnecessary, is presented. In summary, DC/DC-based therapies seem to be promising treatment tools for patients with AML or MDS but ongoing research including trials in animals and humans have to be performed.
由于缺乏治疗选择和高复发率,老年急性髓系白血病(AML)和高级别骨髓增生异常综合征(MDS)患者的预后有限。基于树突状细胞(DC)的免疫疗法似乎是一种有前景的治疗工具。DC是强大的抗原呈递细胞,在固有免疫系统和适应性免疫系统的界面上发挥关键作用。髓系白血病原始细胞可转化为白血病来源的DC(DC),表达共刺激分子以及个体患者的整个白血病抗原库。这些生成的DC是各种免疫反应性细胞的强大刺激剂,并在体外增强抗白血病免疫力。在此,我们回顾了使用“简化”试剂盒从白血病外周血单核细胞以及直接从白血病全血中生成DC/DC的过程,以在体外模拟生理条件。讨论了将DC/DC过继性细胞转移作为一种疫苗接种策略的目的。提出了一种针对髓系白血病患者的新型潜在治疗选择,使用试剂盒可无需进行DC/DC过继性转移。总之,基于DC/DC的疗法似乎是AML或MDS患者有前景的治疗工具,但必须进行包括动物和人体试验在内的持续研究。