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:Immunotherapy on ICU: a narrative review.
Immunotherapy on ICU: a narrative review.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
尽管靶向免疫治疗的发展取得了显著进展,但其所致毒性的作用机制仍知之甚少,限制了预测模型、诊断生物标志物和高效治疗方案的发展。需要进一步研究以确定在 CAR-T 细胞和免疫检查点抑制剂相关毒性中尽量减少使用皮质类固醇的治疗方案。
癌症患者占所有重症监护入院患者的15%,因此了解专科治疗的病理生理学和预期并发症对重症监护临床医生至关重要。针对血液系统恶性肿瘤的CAR-T 细胞疗法以及针对实体器官肿瘤的免疫检查点抑制剂的发展,显著改善了那些肿瘤有应答的患者的预后。本综述旨在使非专科医生了解当前关于CAR-T 细胞疗法和免疫检查点抑制剂治疗恶性疾病所致并发症的病理生理学、诊断和管理概念。
我们对电子数据库进行了检索,以识别文献中相关的同行评审出版物。基础科学、临床试验、队列研究、系统评价、meta分析和指南均符合纳入标准。对摘要进行筛选,以识别与CAR-T 细胞治疗的免疫效应细胞毒性及免疫检查点抑制剂的免疫相关不良事件相关的出版物。
尽管CAR-T 细胞和免疫检查点抑制剂所致毒性的病理生理学仍未完全明了,但针对细胞因子释放综合征等毒性的靶向药物治疗已成功实施。皮质类固醇仍是药物管理的重要组成部分。毒性的诊断在很大程度上仍依赖临床,并且应高度警惕感染性并发症。毒性管理应与患者的主治肿瘤科医生共同进行。
Patients with cancer account for 15% of all admissions to critical care and so an understanding of the pathophysiology and anticipated complications of specialist treatment is essential for the intensive care clinician. The development of chimeric antigen receptor T-cell therapy for haematological malignancies and immune checkpoint inhibitors for solid organ tumours has led to significant improvements in the prognosis of those patients whose tumours respond. This review is intended to provide the non-specialist with an understanding of the current concepts in pathophysiology, diagnosis and management of complications due to chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors for malignant disease.
We performed searches of electronic databases to identify relevant peer-reviewed publications in the literature. Basic science; clinical trials; cohort studies; systematic reviews; meta-analyses; and guidelines were eligible for inclusion. Abstracts were screened to identify publications relevant to immune effector cell toxicities of chimeric antigen receptor T-cell therapy and immune-related adverse events of immune checkpoint inhibitors.
While the pathophysiology for toxicities due to chimeric antigen receptor T-cells and immune checkpoint inhibitors remains incompletely understood, targeted drug therapies have been successfully implemented for toxicities such as cytokine release syndrome. Corticosteroids remain an important component of pharmacological management. The diagnosis of toxicities remains largely clinical, and a high index of suspicion should remain for infective complications. Management of toxicities should be undertaken in conjunction with the patient's primary oncologist.
Despite significant advances in the development of targeted immunotherapy, the mechanism of action for the resultant toxicities remains poorly understood and limits the development of predictive models, diagnostic biomarkers and highly effective treatment options. Further research is needed to identify treatment regimens which minimise the use of corticosteroids in chimeric antigen receptor T-cell and immune checkpoint inhibitor-associated toxicities.
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