抗原特异性免疫治疗技术对急性髓细胞白血病的研究进展

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Update on antigen-specific immunotherapy of acute myeloid leukemia.

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.

抗原特异性免疫治疗技术对急性髓细胞白血病的研究进展

在过去几十年中，在随机药物临床试验中只有少数药物中能够对急性髓细胞白血病患者(AML)有效果，如CD33抗体 - 药物缀合物，吉妥珠单抗奥佐米星（GO）。不用怀疑，这种经验已经强调了抗原特异性免疫治疗在AML中的重要性。很多种类的治疗方案是针对AML细胞表面的不同抗原，目前正在临床试验和早期的临床研究中。另一方面，这些治疗方案包括被动的策略：如未辍和的靶向一种或多种抗原的抗体，药物/毒性蛋白修饰的抗体，放射性核素，或者过继免疫治疗，尤其是CAR-T细胞或者修饰的T细胞受体（TCR），另一方面，还包括活性策略，如接种疫苗。随着GO展现出的治疗效果和其他治疗白血病的治疗手段展现出来的数据，尤其是小分子双特异性抗体和CAR-T细胞技术，未来是光明的。不管如何，仍然有一些重要的问题如靶向抗原的选择，病人群体，确切的治疗方式和支持护理等。解决这些问题最终需要优化AML治疗中的抗原特异性免疫治疗的临床应用，确保这种治疗方式变成一个有效、多功能的工具。

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