Department of Biomedical Engineering, School of Medicine, USA; Institute for Cell Engineering, School of Medicine, USA.
Department of Biomedical Engineering, School of Medicine, USA; Institute for Cell Engineering, School of Medicine, USA; Translational Tissue Engineering Center, USA; Institute for Nanobiotechnology, USA.
Biomaterials. 2021 Jan;268:120584. doi: 10.1016/j.biomaterials.2020.120584. Epub 2020 Dec 5.
T cells are often referred to as the 'guided missiles' of our immune system because of their capacity to traffic to and accumulate at sites of infection or disease, destroy infected or mutated cells with high specificity and sensitivity, initiate systemic immune responses, sterilize infections, and produce long-lasting memory. As a result, they are a common target for a range of cancer immunotherapies. However, the myriad of challenges of expanding large numbers of T cells specific to each patient's unique tumor antigens has led researchers to develop alternative, more scalable approaches. Biomaterial platforms for expansion of antigen-specific T cells offer a path forward towards broadscale translation of personalized immunotherapies by providing "off-the-shelf", yet modular approaches to customize the phenotype, function, and specificity of T cell responses. In this review, we discuss design considerations and progress made in the development of ex vivo and in vivo technologies for activating antigen-specific T cells, including artificial antigen presenting cells, T cell stimulating scaffolds, biomaterials-based vaccines, and artificial lymphoid organs. Ultimate translation of these platforms as a part of cancer immunotherapy regimens hinges on an in-depth understanding of T cell biology and cell-material interactions.
T 细胞通常被称为我们免疫系统的“制导导弹”,因为它们能够在感染或疾病部位运输和积累,具有高度特异性和敏感性地破坏受感染或突变的细胞,引发全身免疫反应,使感染得到清除,并产生持久的记忆。因此,它们是一系列癌症免疫疗法的常见靶点。然而,为每位患者独特的肿瘤抗原大量扩增特定 T 细胞的诸多挑战,促使研究人员开发替代的、更具可扩展性的方法。用于扩增抗原特异性 T 细胞的生物材料平台为广泛转化个性化免疫疗法提供了一条前进的道路,通过提供“现成的”、但可定制的方法来定制 T 细胞反应的表型、功能和特异性。在这篇综述中,我们讨论了在开发用于激活抗原特异性 T 细胞的体外和体内技术方面的设计考虑因素和进展,包括人工抗原呈递细胞、T 细胞刺激支架、基于生物材料的疫苗和人工淋巴器官。这些平台作为癌症免疫治疗方案的一部分的最终转化取决于对 T 细胞生物学和细胞-材料相互作用的深入理解。