CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Chimeric antigen receptor T-cell therapy in acute myeloid leukemia.
Chimeric antigen receptor T-cell therapy in acute myeloid leukemia.
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综述目的:复发/难治性急性髓系白血病(AML)患者的治疗结局仍不理想,亟需新的治疗选择。采用CAR-T 细胞的过继细胞治疗是一个值得关注的潜在方向。 近期发现:目前已有60多项在ClinicalTrials.gov登记的临床试验,正在研究多个可能适用于AML的CAR-T 靶点。首批临床数据刚刚出现,结果不一,再次表明仍需进一步研究。 总结:多项临床试验正在评估CAR-T 细胞过继治疗AML。目前尚未发现AML特异性抗原,因此需要额外策略降低靶向肿瘤同时损伤正常组织的毒性,并提高疗效。研究重点之一是如何在CAR-T 输注后控制其活性。相关策略包括可降解CAR、可诱导CAR、带有自杀开关的CAR,以及双组分模块化CAR。目前数据有限且结果不一,证实不可切换型CAR可能带来持续性毒性。模块化CAR初步结果提示,采用可开启或关闭的模块化设计,可能在维持CAR活性的同时减轻毒性。
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
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