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:Chimeric antigen receptors: "CARs" in the fast lane for rheumatology.
Chimeric antigen receptors: "CARs" in the fast lane for rheumatology.
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血液肿瘤学的最新进展开创了利用嵌合抗原受体(CAR)T细胞介导清除病理性B细胞群体的先河。在这篇综述中,我们讨论了近期采用CAR-T 治疗严重难治性自身免疫病的进展。我们重点阐述了自身免疫模型的独特方面,并回顾了有关风湿病治疗的当前临床数据。
迄今为止,已有几种 CAR-T 获 FDA 批准用于多发性骨髓瘤和 B 细胞恶性肿瘤,并在难治性疾病中展现出非凡的临床反应。鉴于 B 细胞在某些自身免疫性疾病中的核心作用,CAR-T 目前正被探索用于实现无药物缓解诱导,并可能治愈多种风湿性疾病。在自身免疫领域迄今最大的经验中,基于埃尔朗根大学医院团队此前成功治疗一例重度难治性 SLE 患者并接受 CD19-CAR 的经验,Mackensen 等人在同情用药项目中入组了五例患者。在自体 CD19-CAR-T 输注后,他们证明全部五例患者实现了至少 12 个月的无药物临床和实验室缓解,并重建了表达初始表型的 B 细胞。总结:CAR-T 治疗在重度狼疮和其他自身免疫性疾病中显示出显著的无药物反应,因此需要进一步探索和开发。
PURPOSE OF REVIEW: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease.
We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease. RECENT FINDINGS: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases.
The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program.
Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a na ve phenotype. SUMMARY: CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.
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