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:Titrating chimeric antigen receptors on CAR T cells enabled by a microfluidic-based dosage-controlled intracellular mRNA delivery platform.
嵌合抗原受体(CAR)T 细胞疗法在癌症治疗中显示出前所未有的疗效,尤其是在治疗各类血液肿瘤患者时,其中最突出的是 B 细胞急性淋巴细胞白血病。
嵌合抗原受体(CAR)T细胞疗法在癌症治疗中显示出前所未有的疗效,尤其是多种血液肿瘤,包括B细胞急性淋巴细胞白血病。近年来,研究者也在探索CAR-T细胞疗法治疗其他血液系统恶性肿瘤和实体瘤。尽管CAR-T细胞疗法取得显著成功,细胞因子释放综合征(CRS)仍是一种意料之外且可能危及生命的副作用。本研究旨在通过控制CAR-T细胞表面的CAR密度,减少与CRS相关的促炎细胞因子释放。研究显示,利用声电微流控平台可以调节原代T细胞表面的CAR表达密度。该平台通过均匀混合并剪切细胞实现剂量可控的递送,使每个T细胞获得大致相同数量的CAR基因编码mRNA。
Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening. Our aim is to reduce pro-inflammatory cytokine release associated with CRS by controlling CAR surface density on CAR T cells. We show that CAR expression density can be titrated on the surface of primary T cells using an acoustic-electric microfluidic platform. The platform performs dosage-controlled delivery by uniformly mixing and shearing cells, delivering approximately the same amount of CAR gene coding mRNA into each T cell.
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