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:Progressive Multifocal Leukoencephalopathy in Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study.
Progressive Multifocal Leukoencephalopathy in Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study.
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嵌合抗原受体(CAR)T细胞疗法是一种新型免疫治疗方式,在难治性血液系统恶性肿瘤(包括多发性骨髓瘤(MM))中已显示出显著的缓解率。细胞因子释放综合征(CRS)和神经毒性是该疗法已被充分描述的不良反应。CAR-T 细胞疗法接受者由于免疫功能障碍、多线治疗史、细胞输注前淋巴细胞清除性化疗史以及持续性B细胞再生障碍,感染风险也增加。进行性多灶性白质脑病(PML)是一种中枢神经系统机会性疾病,由免疫抑制状态下JC病毒(JCV)再激活引起,可导致发病率和死亡率增加。
在此,我们报告一例接受ciltacabtagene autoleucel治疗难治性MM的患者,其在接受CAR-T 细胞疗法约2个月后出现PML。本病例强调了免疫功能低下患者发生PML的风险,可能与持续性B细胞再生障碍、低丙种球蛋白血症和长期免疫抑制有关,并讨论了治疗方法。PML的治疗主要集中于重建免疫。然而,目前尚未建立足够的PML治疗策略,仍需进一步研究。
Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy.
CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to increased morbidity and mortality.
Here, we present a patient treated with ciltacabtagene autoleucel for refractory MM who presented with PML around 2 months after receiving CAR T-cell therapy. This case emphasizes the risks for the development of PML in immunocompromised patients potentially related to persistent B-cell aplasia, hypogammaglobulinemia, and prolonged immunosuppression and discusses treatment approaches. Treatments for PML are mostly focused on reconstituting immunity.
However, no adequate treatment strategy for PML has yet been established and further research is needed.
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