Immunotherapy in Acute Myeloid Leukemia: Where We Stand.
Immunotherapy in Acute Myeloid Leukemia: Where We Stand.
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DOI：
10.3389/fonc.2021.656218
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发表时间：
2021
影响因子：
4.7
通讯作者：
Curti A
中科院分区：
文献类型：
--
作者：
Isidori A;Cerchione C;Daver N;DiNardo C;Garcia-Manero G;Konopleva M;Jabbour E;Ravandi F;Kadia T;Burguera AF;Romano A;Loscocco F;Visani G;Martinelli G;Kantarjian H;Curti A
在过去的几年里，我们对急性髓细胞白血病（AML）发病机制的认识不断提高，加速了新药的发现和创新治疗方法的开发。免疫系统在AML发展、生长和复发中的作用越来越受到关注。对AML原始细胞诱导的免疫逃逸和系统耐受有了更好的理解。利用T细胞在实体瘤和某些血液恶性肿瘤中的力量的免疫疗法的非凡成功为这一研究领域提供了新的刺激。因此，已经做出重大努力来开发用于治疗AML患者的免疫疗法。即使在异基因干细胞移植（allo-SCT）后，白血病干细胞的持续存在仍然是AML患者治愈道路上的一个主要障碍。目前正在一线、复发性/难治性、allo-SCT后和微小残留疾病/维持环境中进行几项基于免疫的治疗的临床试验，旨在改善AML患者的生存期。本综述总结了基于免疫的治疗方式的可用数据，如单克隆抗体（裸抗体和结合抗体），T细胞增殖剂，过继性T细胞治疗，过继性NK治疗，通过PD-1/PD-L1，CTLA 4，TIM 3和通过CD 47/SIRPa轴的巨噬细胞检查点阻断的检查点阻断，以及白血病疫苗。将临床结果与生物免疫学发现相结合，可能再加上预测反应的生物标志物的发现，将有望使我们能够确定AML免疫治疗的最佳方法。
In the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interest. A better understanding of immunological escape and systemic tolerance induced by AML blasts has been achieved. The extraordinary successes of immune therapies that harness the power of T cells in solid tumors and certain hematological malignancies have provided new stimuli in this area of research. Accordingly, major efforts have been made to develop immune therapies for the treatment of AML patients. The persistence of leukemia stem cells, representing the most relevant cause of relapse, even after allogeneic stem cell transplant (allo-SCT), remains a major hurdle in the path to cure for AML patients. Several clinical trials with immune-based therapies are currently ongoing in the frontline, relapsed/refractory, post-allo-SCT and minimal residual disease/maintenance setting, with the aim to improve survival of AML patients. This review summarizes the available data with immune-based therapeutic modalities such as monoclonal antibodies (naked and conjugated), T cell engagers, adoptive T-cell therapy, adoptive-NK therapy, checkpoint blockade via PD-1/PD-L1, CTLA4, TIM3 and macrophage checkpoint blockade via the CD47/SIRPa axis, and leukemia vaccines. Combining clinical results with biological immunological findings, possibly coupled with the discovery of biomarkers predictive for response, will hopefully allow us to determine the best approaches to immunotherapy in AML.
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影响因子：
11.4
作者：
Amadori, S;Suciu, S;de Witte, T
通讯作者：
de Witte, T
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