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3D 打印晶格作为 T 细胞治疗的激活和扩增平台。

3D printed lattices as an activation and expansion platform for T cell therapy.

机构信息

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Future Industries Institute, University of South Australia, Adelaide, Australia; Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, Australia.

Molecular Immunology, Dept. of Gastroenterology, Women's and Children's Hospital, Adelaide, Australia; Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, Australia.

出版信息

Biomaterials. 2017 Sep;140:58-68. doi: 10.1016/j.biomaterials.2017.05.009. Epub 2017 Jun 7.

Abstract

One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation. This 3D technology platform facilitate the expansion of therapeutic human T cell subsets, including regulatory, effector, and cytotoxic T cells while maintaining the correct phenotype. Lentiviral gene delivery to T cells is enhanced in the presence of the lattices. Incorporation of the lattice format into existing cell culture vessels such as the G-Rex system is feasible. This cell expansion platform is user-friendly and expedites cell recovery and scale-up, making it ideal for translating T cell therapies from bench to bedside.

摘要

细胞治疗的可负担性和可及性面临的最大障碍之一是细胞扩增至临床相关数量的成本和难度。免疫疗法预防自身免疫性疾病、耐受器官移植或靶向癌症,关键依赖于专门 T 细胞群体的扩增。我们设计了具有高度组织化微尺度结构的 3D 打印细胞培养格子,通过等离子体聚合进行功能化,以结合触发细胞增殖的单克隆抗体。这种 3D 技术平台促进了治疗性人 T 细胞亚群的扩增,包括调节性、效应性和细胞毒性 T 细胞,同时保持正确的表型。在存在格子的情况下,慢病毒基因向 T 细胞的传递得到增强。将格子形式纳入现有的细胞培养容器中,如 G-Rex 系统,是可行的。这种细胞扩增平台易于使用,加快了细胞回收和扩大规模的速度,使其成为将 T 细胞疗法从实验室转化为临床的理想选择。

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