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:A regenerative and programmable iPSC-derived platelet platform for universal drug delivery and immunotherapy.
基于血小板的药物递送系统在癌症治疗中日益受到关注,但其更广泛的应用受到来源有限和基因可修饰性差的制约。
基于血小板的药物递送系统在癌症治疗中日益受到关注,但其更广泛的应用受到来源有限和基因修饰性差的限制。在此,我们建立了一个源自人诱导多能干细胞的可再生且可编程的基于血小板的药物递送平台。通过工程化改造这些诱导多能干细胞以表达共刺激信号4-1BBL,我们生成了呈递4-1BBL的诱导血小板(BBL1-iPLTs),其充当人工抗原呈递细胞。在体外,BBL1-iPLTs显著增强了T细胞活化和增殖,并增强了对多种类型癌细胞的细胞毒性活性,包括白血病细胞和实体瘤细胞系,凸显了其广泛的治疗潜力。在急性淋巴细胞白血病小鼠模型中,全身递送BBL1-iPLTs有效增强了第一代CD19-CAR-T 细胞活性并抑制了肿瘤进展。这项工作为下一代癌症免疫治疗及其他领域建立了一个可再生、可基因工程化且可临床转化的血小板平台。
Platelet-based drug-delivery systems have garnered increasing attention for cancer treatment, yet their broader application is hindered by the limited source and poor genetic modifiability. Here, we established a regenerative and programmable platelet-based drug-delivery platform derived from human-induced pluripotent stem cells. By engineering these induced pluripotent stem cells to express a co-stimulatory signal, 4-1BBL, we generated 4-1BBL-presenting induced platelets (BBL1-iPLTs) that act as artificial antigen-presenting cells. In vitro, BBL1-iPLTs markedly enhanced T cell activation and proliferation and augmented cytotoxic activity against several types of cancer cells, including leukemia cells and solid tumor cell lines, underscoring their broad therapeutic potential. In murine models of acute lymphoblastic leukemia, systemic delivery of BBL1-iPLTs effectively boosted first-generation CD19-chimeric antigen receptor T cell activity and suppressed tumor progression. This work establishes a renewable, genetically engineerable, and clinically translatable platelet platform for next-generation cancer immunotherapy and beyond.
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