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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Pathogenesis, Diagnosis, and Management of Cytokine Release Syndrome in Patients with Cancer: Focus on Infectious Disease Considerations.
Pathogenesis, Diagnosis, and Management of Cytokine Release Syndrome in Patients with Cancer: Focus on Infectious Disease Considerations.
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细胞因子释放综合征(CRS)是CAR-T 细胞疗法和双特异性T细胞衔接器(BiTE)等免疫疗法引发的一种高炎症状态。CRS表现为细胞因子过量释放,常类似感染和炎症性疾病,使诊断及治疗复杂化。治疗CRS所用免疫抑制疗法还会进一步增加继发感染风险。
系统检索PubMed和EMBASE,检索词涉及“细胞因子释放综合征”“细胞因子风暴”“感染”和“管理”。纳入描述CRS相关感染并发症、诊断模拟疾病或治疗方法的研究。
在19,634篇研究中审阅了2572篇摘要。CAR-T 治疗后感染率最高达23%,BiTE治疗后达24%。病原体包括革兰阳性和革兰阴性细菌、疱疹病毒(如CMV、HSV)、真菌(如念珠菌、曲霉菌)及寄生虫(如刚地弓形虫)。CRS模拟症还包括非感染性炎症综合征。鉴别仍具挑战,但细胞因子谱和铁蛋白、CRP、可溶性IL-2受体等生物标志物可能有助诊断。治疗包括托珠单抗、皮质类固醇和经验性抗微生物药物。预防策略的报道不一致。
有效管理CRS需早期识别、与感染性模拟疾病鉴别,并加强肿瘤科和感染科协作。多学科、协作且结构化的管理方法,包括感染科专门参与及治疗前评估,对于优化CRS管理和患者结局至关重要。
Background: Cytokine Release Syndrome (CRS) is a hyperinflammatory state triggered by immune therapies like CAR T-cell therapy and bispecific T-cell engagers (BiTEs). Characterized by excessive cytokine release, CRS often mimics infectious and inflammatory conditions, complicating diagnosis and treatment. Immunosuppressive therapies used for CRS further elevate the risk of secondary infections. Methods: A systematic search of PubMed and EMBASE was conducted using terms related to "cytokine release syndrome", "cytokine storm", "infections", and "management". Studies were included if they described infectious complications, diagnostic mimics, or therapeutic approaches related to CRS. Results: Of 19,634 studies, 2572 abstracts were reviewed. Infections occurred in up to 23% of patients post-CAR T therapy and 24% post-BiTE therapy.
Pathogens included gram-positive and gram-negative bacteria, herpesviruses (e. g. , CMV, HSV), fungi (e. g. , Candida , Aspergillus ), and parasites (e. g. , Toxoplasma gondii). CRS mimics also included non-infectious inflammatory syndromes. Differentiation remains challenging, but cytokine profiling and biomarkers (e. g. , ferritin, CRP, sIL-2R ) may aid in diagnosis. Treatments included tocilizumab, corticosteroids, and empiric antimicrobials.
Prophylactic strategies were inconsistently reported. Conclusions: Effective CRS management requires early recognition, differentiation from infectious mimics, and collaboration between oncology and infectious disease (ID) specialists. A multidisciplinary, collaborative, and structured approach, including dedicated ID input and pre-treatment evaluation, is essential for optimizing CRS management and patient outcomes.
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