嵌合抗原受体T细胞疗法的不良反应与治疗

Toxicity and management in chimeric antigen receptor T-cell therapy

T细胞可以通过表达嵌合抗原受体(CAR)对肿瘤靶细胞进行识别和杀灭。CART细胞治疗在血液系统肿瘤中疗效显著,但是在实体瘤中疗效有限。然而CART细胞治疗也可引起预期或不能预期的不良反应,包括细胞因子释放综合征、神经系统毒性、脱靶效应和过敏反应。理论上的不良反应还包括克隆扩增继发插入癌变、移植物抗宿主病和靶抗原不能识别。减轻不良反应已成为这一新兴技术成功应用的关键。文章综述CART细胞治疗的不良反应,以及理论上存在的不良反应及应对策略。

T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor(CAR).Most notably,CAR T cells have demonstrated its clinical efficacy in hematologic malignancies with evident responses whentargeting solid tumors.However,CAR T cells therapy also has the capacity to elicit expected and unexpected toxicities includingcytokine release syndrome,neurologic toxicity,“on target/off tumor”recognition,and anaphylaxis.Theoretical toxicities includeclonal expansion secondary to insertional oncogenesis,graft versus host disease,and off-target antigen recognition.Abrogatingtoxicity has become a critical step in the successful application of this emerging technology.To this end,we review the reportedand theoretical toxicities of CAR T cells therapy and strategies to cope with it.