Georgiadis Christos, Preece Roland, Qasim Waseem
University College London Great Ormond Street Institute of Child Health, Zayed Centre for Research, 20 Guilford Street, London WC1N 1DZ, UK.
University College London Great Ormond Street Institute of Child Health, Zayed Centre for Research, 20 Guilford Street, London WC1N 1DZ, UK.
Mol Ther. 2025 Jun 4;33(6):2426-2440. doi: 10.1016/j.ymthe.2025.03.040. Epub 2025 Mar 27.
Ready-made banks of allogeneic chimeric antigen receptor (CAR) T cells, produced to be available at the time of need, offer the prospect of accessible and cost-effective cellular therapies. Various strategies have been developed to overcome allogeneic barriers, drawing on cell engineering platforms including RNA interference, protein-based restriction, and genome editing, including RNA-guided CRISPR-Cas and base editing tools. Alloreactivity and the risk of graft-versus-host disease from non-matched donor cells have been mitigated by disruption of αβ-T cell receptor expression on the surface of T cells and stringent removal of any residual αβ-T cell populations. In addition, host-mediated rejection has been tackled through a combination of augmented lymphodepletion and cell engineering strategies that have allowed infused cells to evade immune recognition or conferred resistance to lymphodepleting agents to promote persistence and expansion of effector populations. Early-phase studies using off-the-shelf universal donor CAR T cells have been undertaken mainly in the context of blood malignancies, where emerging data of clinical responses have supported wider adoption and further applications. These developments offer the prospect of alternatives to current autologous approaches through the emerging application of genome engineering solutions to improve safety, persistence, and function of universal donor products.
现成的异体嵌合抗原受体（CAR）T细胞库在需要时即可提供，为可及且具成本效益的细胞疗法带来了希望。人们已开发出各种策略来克服异体障碍，利用包括RNA干扰、基于蛋白质的限制以及基因组编辑（包括RNA引导的CRISPR-Cas和碱基编辑工具）在内的细胞工程平台。通过破坏T细胞表面的αβ-T细胞受体表达以及严格去除任何残留的αβ-T细胞群体，已减轻了来自不匹配供体细胞的同种异体反应性和移植物抗宿主病风险。此外，通过增强淋巴细胞清除和细胞工程策略的组合来应对宿主介导的排斥反应，这些策略使注入的细胞能够逃避免疫识别或赋予对淋巴细胞清除剂的抗性，以促进效应细胞群体的存活和扩增。使用现成的通用供体CAR T细胞的早期研究主要在血液恶性肿瘤背景下进行，临床反应的新数据支持了其更广泛的应用和进一步应用。这些进展通过基因组工程解决方案的新兴应用为当前自体方法提供了替代方案，以提高通用供体产品的安全性、存活时间和功能。
