Guarnera Luca, Bravo-Perez Carlos, Visconte Valeria
Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
Bioengineering (Basel). 2023 Oct 20;10(10):1228. doi: 10.3390/bioengineering10101228.
In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies, such as antibody-based therapy, checkpoint inhibitors, and chimeric antigen receptor strategies, successfully tested in other hematologic malignancies, were very high. The inherent characteristics of AML blasts hampered the development of these treatments, and the path of immunotherapy in AML has been bumpy. Herein, we provide a detailed review of potential antigenic targets, available data from pre-clinical and clinical trials, and future directions of immunotherapies in AML.
在过去二十年里,我们见证了急性髓系白血病(AML)治疗和预后方面的范式转变,这得益于新型高效药物的引入或旧疗法的优化改进,如吉妥珠单抗奥唑米星、CPX 3-5-1、低甲基化药物和维奈克拉,异基因造血干细胞移植预处理方案的优化以及支持治疗的改善。然而,非M3型和非核心结合因子AML的长期生存率仍然很低。因此,对于最近开发的免疫疗法,如基于抗体的疗法、检查点抑制剂和嵌合抗原受体策略(这些疗法已在其他血液系统恶性肿瘤中成功进行了测试),人们寄予了很高的期望。AML原始细胞的固有特性阻碍了这些治疗方法的发展,AML免疫治疗之路坎坷不平。在此,我们详细综述了AML潜在的抗原靶点、临床前和临床试验的现有数据以及免疫治疗的未来发展方向。