AvenCell Europe GmbH, Dresden, Germany.
Division of Hematology, Oncology and Stem Cell Transplantation, Medical Clinic I, Department of Medicine I, University Hospital Carl Gustav Carus.
Curr Opin Hematol. 2022 Mar 1;29(2):74-83. doi: 10.1097/MOH.0000000000000703.
Treatment outcome of relapsed or refractory AML patients remains dismal and new treatment options are needed. Adoptive cell therapy using CAR-T cells is a potentially interesting approach in this.
Several potentially interesting AML targets are being investigated with CAR-T therapy with over 60 clinical trials listed on clinicaltrials.gov. The first clinical data are only just emerging with mixed results, once more proving that further research is needed.
Adoptive cell therapy using chimeric antigen receptor T cells is being investigated in AML through many clinical trials. So far, no AML-specific antigen has been identified, requiring additional strategies to mitigate on-target off-tumor toxicity and to increase efficacy. Focus point is to acquire control over the CAR T cells once administered. Strategies to do so include biodegradable CARs, inducible CARs, suicide-switch containing CARs and two-component modular CARs. Limited and mixed results are available, confirming the risk of lasting toxicity for nonswitchable CARs. Initial results of modular CARs suggest toxicity can be mitigated whilst maintaining CAR activity by the use of modular CAR concepts that allows for 'ON' and 'OFF' switching.
复发或难治性 AML 患者的治疗结果仍然不佳，需要新的治疗方法。嵌合抗原受体 T 细胞（CAR-T）的过继细胞疗法是一种很有前景的方法。
已有 60 多项临床试验在 clinicaltrials.gov 上列出，对多种潜在的 AML 靶点进行了 CAR-T 治疗的研究。首批临床数据刚刚出现，结果喜忧参半，这再次证明需要进一步研究。
通过多项临床试验，嵌合抗原受体 T 细胞的过继细胞疗法正在 AML 中进行研究。到目前为止，还没有确定 AML 特异性抗原，这需要额外的策略来减轻靶标肿瘤外毒性并提高疗效。重点是在给药后获得对 CAR-T 细胞的控制。实现这一目标的策略包括可生物降解的 CAR、诱导型 CAR、包含自杀开关的 CAR 和双组分模块化 CAR。目前获得的结果有限且喜忧参半，证实了不可切换的 CAR 存在持久毒性的风险。模块化 CAR 的初步结果表明，通过使用允许“开”和“关”切换的模块化 CAR 概念，可以减轻毒性，同时保持 CAR 活性。
