决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Neurological complications of current and emerging CAR-T cell therapies.
利用患者个体的免疫系统增强抗肿瘤反应一直是肿瘤学长期以来的目标。
利用个体患者自身免疫系统增强抗肿瘤应答,长期以来一直是肿瘤学的目标。目前已有多种免疫调节或免疫增强疗法获FDA批准或正在开发中,它们采用不同策略调动患者自身免疫系统。其中一种疗法是CAR-T 细胞疗法,即通过基因工程改造T细胞,使其靶向肿瘤细胞上的特定抗原。目前多种CAR-T产品已获批临床使用,并在血液系统恶性肿瘤中取得显著且持久的应答。但治疗癌症的疗效也伴随并发症风险,包括较高的神经系统并发症发生率。基于细胞疗法在血液系统肿瘤中的成功,这些技术正被用于实体恶性肿瘤(包括中枢神经系统肿瘤)以及非肿瘤性疾病(如自身免疫病)的研究。随着新的CAR-T疗法设计并进入临床实践,评估其神经毒性风险,并开发预防或治疗相关并发症的疗法十分重要。本文概述这些新型强效细胞疗法可能引发的急性及潜在长期神经系统并发症,重点讨论新兴CAR-T技术、相关神经毒性及降低此类并发症的潜在干预措施。
Harnessing an individual patient's immune system to enhance anti-tumor responses has been a long-standing goal in oncology. Multiple immune modulating or immune enhancing therapies have been FDA approved or are under development, utilizing varying strategies to engage the patient's own immune system. One such therapy is chimeric antigen receptor T-cell therapy (CAR-T), in which T-cells are genetically engineered to target specific antigens present on tumor cells. Multiple CAR-T products are currently approved for clinical use, with impressive and durable responses seen in hematologic cancers. With their efficacy for treating cancer comes the risk of complications, including a high frequency of neurologic complications. Based on the success seen with cellular therapies in hematologic cancers, these technologies are being tested for both the use in solid malignancies, including central nervous system tumors, and for their application in non-neoplastic conditions such as autoimmune diseases. As new CAR-T therapies are designed and introduced into clinical practice, it will be important to assess their risks of neurologic toxicity and to develop therapies to either prevent or treat these complications. Here, we provide an overview of the acute and potentially long-term neurologic complications encountered with these novel and powerful cellular therapies, focusing on emerging CAR-T technologies, their associated neurotoxicities and potential interventions to limit such neurologic complications.
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