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:Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.
Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.
值得注意的是,使用 SynVACs 激活并扩增嵌合抗原受体(CAR)T 细胞可使 CAR 转导效率达到约 90%,并大幅增加 T 记忆干细胞。
利用合成抗原呈递细胞活化并扩增经工程化改造的T细胞以治疗癌症,通常难以获得疗效和持久性均理想的治疗方案。本文介绍一种高通量微流控系统,可制备模拟抗原呈递细胞黏弹性及T细胞活化特性的合成细胞。与刚性或弹性微球相比,合成黏弹性T细胞活化细胞(SynVAC)显著促进人CD8+ T细胞扩增,并抑制调节性T细胞形成。值得注意的是,使用SynVAC活化并扩增嵌合抗原受体(CAR)T细胞,可使CAR转导效率达到约90%,并显著增加记忆干细胞样T细胞。工程化CAR T细胞在人体淋巴瘤小鼠模型中清除肿瘤细胞,在人卵巢癌异种移植小鼠中抑制肿瘤生长,同时具有更长的持续存留时间并降低肿瘤复发风险。研究结果凸显黏弹性在T细胞工程化中的关键作用,并显示SynVAC在癌症治疗中的应用潜力。
The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8 + T cells and to the suppression of the formation of regulatory T cells. Notably, activating and expanding chimaeric antigen receptor (CAR) T cells with SynVACs led to a CAR-transduction efficiency of approximately 90% and to substantial increases in T memory stem cells. The engineered CAR T cells eliminated tumour cells in a mouse model of human lymphoma, suppressed tumour growth in mice with human ovarian cancer xenografts, persisted for longer periods and reduced tumour-recurrence risk. Our findings underscore the crucial roles of viscoelasticity in T-cell engineering and highlight the utility of SynVACs in cancer therapy.
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