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:Injectable bioinstructive microfoam for rapid bedside/in vivo programming of CAR-T cells.
尽管嵌合抗原受体(CAR)T细胞疗法已经改变了血液系统恶性肿瘤的治疗格局,并正在被探索用于实体瘤,但其广泛应用仍受限于高昂的成本、复杂的生产要求、漫长的等待时间以及不平等的可及性。
嵌合抗原受体(CAR)T 细胞疗法已改变血液系统恶性肿瘤的治疗格局,也正在实体瘤中探索;但其广泛应用仍受高昂费用、复杂的制备要求、漫长的等待时间以及可及性不平等等因素限制。本文介绍一种基于甲基纤维素的基因治疗微泡沫,可在采血后数小时内快速制备 CAR-T 细胞,用于皮下注射。具体而言,我们证明,微泡沫促使 T 细胞与载体共定位,从而实现高效的 CAR 基因转移。皮下注射后,新编程的 CAR-T 细胞可在全身播散,并在淋巴瘤和肝细胞癌小鼠异种移植模型中使远端肿瘤消退,其抗肿瘤活性与常规制备的 CAR-T 细胞相当。该平台为无菌封闭系统,无需长时间细胞培养、集中式生产设施或洁净室细胞生产。上述发现为一种简化的 CAR-T 制备策略提供了概念验证;与传统 CAR-T 疗法相比,该策略有望降低制备复杂度和基础设施要求,并提高细胞免疫疗法的可及性。
While chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of hematological malignancies and are being explored for solid tumors, their widespread use remains limited by high costs, complex manufacturing requirements, long wait times, and unequal access. Here, we describe a methylcellulose-based gene therapy microfoam that enables rapid generation of CAR-T cells for subcutaneous administration within hours of blood collection. Specifically, we demonstrate that colocalization of T cells and vector within the foam promotes efficient CAR gene transfer. Following subcutaneous injection, newly programmed CAR-T cells disperse systemically and mediate regression of distal tumors in mouse xenograft models of lymphoma and hepatocellular carcinoma, with antitumor activity comparable to conventionally manufactured CAR-T cells. The platform operates as a sterile closed system and does not require prolonged cell culture, centralized manufacturing facilities, or cleanroom-based cell production. These findings establish proof of concept for a simplified CAR-T generation strategy that may reduce manufacturing complexity and infrastructure requirements relative to conventional CAR-T therapy while improving the accessibility of cellular immunotherapies.
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