小柯机器人

美国北卡罗来纳大学Yevgeny Brudno课题组在研究中取得进展。他们研发出可用于体内快速产生和释放嵌合抗原受体(CAR)-T细胞的生理性植入式支架。相关论文于2022年3月24日发表于国际学术期刊《自然-生物技术》杂志。

研究人员研发了一种用于T细胞工程和释放(MASTER)的可植入多功能藻酸盐支架，它简化了体内CAR-T细胞的制造并将处理时间缩短到一天。当用人外周血单核细胞和编码CD19的逆转录病毒颗粒接种时，MASTER为病毒载体介导的基因转移提供了适当的界面，并在皮下植入后，介导小鼠体内功能性CAR-T细胞的释放。研究进一步证明，在小鼠淋巴瘤异种移植模型中，体内产生的CAR-T细胞可进入血液并控制远端肿瘤生长，比传统CAR-T细胞更具持久性。MASTER通过快速产生和降低此类疗法的复杂性和所需资源从而改变CAR-T细胞疗法。

据介绍，尽管在临床上取得了成功，但使用CAR-T细胞疗法治疗B细胞恶性肿瘤仍受到冗长、昂贵和劳动密集型离体制造程序的限制，这同时也可能导致细胞产品具有异质成分。

附：英文原文

Title: Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells

Author: Agarwalla, Pritha, Ogunnaike, Edikan A., Ahn, Sarah, Froehlich, Kristen A., Jansson, Anton, Ligler, Frances S., Dotti, Gianpietro, Brudno, Yevgeny

Issue&Volume: 2022-03-24

Abstract: Despite their clinical success, chimeric antigen receptor (CAR)-T cell therapies for B cell malignancies are limited by lengthy, costly and labor-intensive ex vivo manufacturing procedures that might lead to cell products with heterogeneous composition. Here we describe an implantable Multifunctional Alginate Scaffold for T Cell Engineering and Release (MASTER) that streamlines in vivo CAR-T cell manufacturing and reduces processing time to a single day. When seeded with human peripheral blood mononuclear cells and CD19-encoding retroviral particles, MASTER provides the appropriate interface for viral vector-mediated gene transfer and, after subcutaneous implantation, mediates the release of functional CAR-T cells in mice. We further demonstrate that in vivo-generated CAR-T cells enter the bloodstream and control distal tumor growth in a mouse xenograft model of lymphoma, showing greater persistence than conventional CAR-T cells. MASTER promises to transform CAR-T cell therapy by fast-tracking manufacture and potentially reducing the complexity and resources needed for provision of this type of therapy. Implantable scaffolds rapidly generate and release anti-tumor CAR-T cells in mice.

DOI: 10.1038/s41587-022-01245-x

Source: https://www.nature.com/articles/s41587-022-01245-x

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
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投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex