Recent developments in immunotherapy of acute myeloid leukemia.
Recent developments in immunotherapy of acute myeloid leukemia.
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DOI：
10.1186/s13045-017-0505-0
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发表时间：
2017-07-25
影响因子：
28.5
通讯作者：
Subklewe M
中科院分区：
文献类型：
--
作者：
Lichtenegger FS;Krupka C;Haubner S;Köhnke T;Subklewe M
在过去的十年中，新的免疫治疗药物在临床实践中的出现已经彻底改变了肿瘤治疗，无论是在肿瘤学还是血液学。将免疫治疗概念转移到急性髓性白血病（AML）的治疗受到疾病的各种特征的阻碍，包括非白血病限制性靶抗原表达谱，低内源性免疫反应，以及白血病母细胞对免疫反应的内在抵抗机制。然而，在过去几年中，这一领域取得了相当大的进展。在这篇文章中，我们回顾了最近的发展和五个目前最突出的免疫治疗概念的现状：(1)抗体-药物偶联物，(2)T细胞招募抗体构建，(3)嵌合抗原受体（CAR） T细胞，(4)检查点抑制剂，(5)树突状细胞疫苗接种。我们专注于迄今为止已发表的临床数据，包括新诊断和难治性/复发性AML，但忽略了与造血干细胞移植相结合的免疫治疗概念。此外，我们还纳入了目前正在进行或最近完成但仍未完全发表其结果的重要临床试验。虽然每个概念都有其独特的优点和固有的问题，但AML的免疫治疗领域似乎已经取得了一些重要的进展。目前正在进行的试验的结果将揭示进一步发展的方向，包括结合两个或更多这些概念的方法。
The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years. Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1) antibody-drug conjugates, (2) T cell-recruiting antibody constructs, (3) chimeric antigen receptor (CAR) T cells, (4) checkpoint inhibitors, and (5) dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results. While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts.
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