Abadir Edward, Gasiorowski Robin E, Silveira Pablo A, Larsen Stephen, Clark Georgina J
Dendritic Cell Research, ANZAC Research Institute, Concord 2139, NSW, Australia.
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown 2050, NSW, Australia.
J Clin Med. 2020 Feb 18;9(2):554. doi: 10.3390/jcm9020554.
From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for AML at preclinical and clinical levels. Gemtuzumab Ozogamicin has demonstrated hematologic toxicity, but the challenge of preserving normal hematopoiesis has become more apparent with the development of increasingly potent immunotherapies. To date, no single surface molecule has been identified that is able to differentiate AML from Hematopoietic Stem and Progenitor Cells (HSPC). Attempts have been made to spare hematopoiesis by targeting molecules expressed only on later myeloid progenitors as well as AML or using toxins that selectively kill AML over HSPC. Other strategies include targeting aberrantly expressed lymphoid molecules or only targeting monocyte-associated proteins in AML with monocytic differentiation. Recently, some groups have accepted that stem cell transplantation is required to access potent AML immunotherapy and envision it as a rescue to avoid severe hematologic toxicity. Whether it will ever be possible to differentiate AML from HSPC using surface molecules is unclear. Unless true specific AML surface targets are discovered, stem cell transplantation could be required to harness the true potential of immunotherapy in AML.
从单克隆抗体（mAb）到嵌合抗原受体（CAR）T细胞，免疫疗法提高了针对B细胞恶性肿瘤的治疗效果。但急性髓系白血病（AML）并非如此。血液学毒性在临床前和临床水平上限制了现代免疫疗法用于AML的潜力。吉妥单抗已显示出血液学毒性，但随着免疫疗法效力的不断提高，保护正常造血功能的挑战变得更加明显。迄今为止，尚未发现能够区分AML与造血干细胞和祖细胞（HSPC）的单一表面分子。人们尝试通过靶向仅在晚期髓系祖细胞以及AML上表达的分子，或使用能选择性杀死AML而非HSPC的毒素来保留造血功能。其他策略包括靶向异常表达的淋巴分子，或仅靶向具有单核细胞分化的AML中与单核细胞相关的蛋白。最近，一些研究团队认为需要进行干细胞移植才能获得有效的AML免疫疗法，并将其视为避免严重血液学毒性的一种挽救措施。目前尚不清楚是否有可能利用表面分子区分AML与HSPC。除非发现真正特异性的AML表面靶点，否则可能需要进行干细胞移植才能发挥免疫疗法在AML中的真正潜力。
