Buckley Sarah A, Walter Roland B
Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA, USA.
Curr Hematol Malig Rep. 2015 Jun;10(2):65-75. doi: 10.1007/s11899-015-0250-9.
Among the few drugs that have shown a benefit for patients with acute myeloid leukemia (AML) in randomized clinical trials over the last several decades is the CD33 antibody-drug conjugate, gemtuzumab ozogamicin (GO). Undoubtedly, this experience has highlighted the value of antigen-specific immunotherapy in AML. A wide variety of therapeutics directed against several different antigens on AML cells are currently explored in preclinical and early clinical studies. On the one hand, these include passive strategies such as unconjugated antibodies targeting one or more antigens, antibodies armed with drugs, toxic proteins, or radionuclides, or adoptive immunotherapies, in particular utilizing T cells engineered to express chimeric antigen receptors (CARs) or modified T cell receptor (TCR) genes; on the other hand, these include active strategies such as vaccinations. With the documented benefit for GO and the emerging data with several classes of therapeutics in other leukemias, in particular small bispecific antibodies and CAR T cells, the future is bright. Nevertheless, a number of important questions related to the choice of target antigen(s), patient population, exact treatment modality, and supportive care needs remain open. Addressing such questions in upcoming studies will ultimately be required to optimize the clinical use of antigen-specific immunotherapies in AML and ensure that such treatments become an effective, versatile tool for this disease for which the outcomes have remained unsatisfactory in many patients.
在过去几十年的随机临床试验中，对急性髓系白血病（AML）患者显示出益处的少数药物中，有CD33抗体药物偶联物吉妥单抗奥唑米星（GO）。毫无疑问，这一经验凸显了抗原特异性免疫疗法在AML中的价值。目前，针对AML细胞上几种不同抗原的多种治疗方法正在临床前和早期临床研究中进行探索。一方面，这些方法包括被动策略，如靶向一种或多种抗原的未偶联抗体、携带药物、毒性蛋白或放射性核素的抗体，或过继性免疫疗法，特别是利用经过工程改造以表达嵌合抗原受体（CAR）或修饰的T细胞受体（TCR）基因的T细胞；另一方面，这些方法包括主动策略，如疫苗接种。鉴于GO已证明的益处以及其他白血病中几类治疗方法的新数据，特别是小型双特异性抗体和CAR T细胞，前景光明。然而，与靶抗原的选择、患者群体、确切的治疗方式以及支持性护理需求相关的一些重要问题仍未解决。在未来的研究中解决这些问题最终将是优化AML中抗原特异性免疫疗法临床应用的必要条件，并确保此类治疗成为这种疾病的有效、通用工具，而目前许多患者的治疗效果仍不尽人意。
