CAR-T治疗相关不良反应的中医病因病机及治法

Etiology,pathogeny and treatment in traditional Chinese medicine for adverse reactions of chimeric antigen receptor T-cell therapy

作为肿瘤治疗的新疗法,嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)治疗在为患者带来福音的同时,也引发了与放射治疗、化学治疗、靶向治疗及免疫治疗等常规抗肿瘤治疗不同的不良反应,其中以包括发热、腹泻等症状在内的细胞因子释放综合征和包括头痛、癫痫等神经系统毒性症状在内的CAR-T相关性脑病为主。根据CAR-T治疗相关的不良反应,通过中医基础理论及中药药性理论尝试对CAR-T治疗进行中药性能分析,认为其药物性能四气中属温热之品,五味中属辛甘,趋向升浮,归于心、肝经,其引发的不良反应的主要病因为特殊的“自身免疫药毒”,主要的病理机制为风火痰瘀合而为病,上扰心脑,下侵肠腑。

As a novel cancer treatment,chimeric antigen receptor T-cell(CAR-T)therapy has brought benefits to patients,but has caused adverse reactions distinct from conventional anti-tumor treatments like radio therapy,chemotherapy,targeted therapy,and immunotherapy.The primary adverse reactions include cytokine release syndrome,which encompasses symptoms such as fever and diarrhea,and CAR-T-related encephalopathy,which includes neurological toxicities like headache and seizures.In analyzing the adverse reactions related to CAR-T cell therapy from the perspective of traditional Chinese medicine basic theory and the theory of herbal properties,CAR-T therapy is considered to possess properties of warmth within the four qi and belongs to the sweet and pungent tastes among the five flavors.It tends to ascend and float,is associated with the heart and liver meridians,and is the result of a unique from of“autoimmune drug toxicity”.The primary pathogenies involve the combination of pathogenic wind,fire,phlegm and blood stasis,meanwhile the heart,brain and gut are affected.