The efficacy of adoptive T-cell therapies based on chimaeric antigen receptors (CARs) is limited by the poor proliferation and persistence of the engineered T cells. Here we show that a subcutaneously injected biodegradable scaffold that facilitates the infiltration and egress of specific T-cell subpopulations, which forms a microenvironment mimicking features of physiological T-cell activation, enhances the antitumour activity of pre-administered CAR-T cells. CAR-T-cell expansion, differentiation and cytotoxicity were driven by the scaffold’s incorporation of co-stimulatory bound ligands and soluble molecules, and depended on the types of co-stimulatory molecules and the context in which they were presented. In mice with aggressive lymphoma, a single, local injection of the scaffold following non-curative CAR-T-cell dosing led to more persistent memory-like T cells and extended animal survival. Injectable biomaterials with optimized ligand presentation may boost the therapeutic performance of CAR-T-cell therapies.

基于嵌合抗原受体 (CAR) 的过继性 T 细胞疗法的疗效受到工程化 T 细胞增殖和持久性差的限制。在这里，我们展示了一种皮下注射的生物可降解支架，可促进特定 T 细胞亚群的浸润和流出，形成模仿生理 T 细胞激活特征的微环境，增强预给药 CAR-T 细胞的抗肿瘤活性。 CAR-T 细胞的扩增、分化和细胞毒性是由共刺激结合配体和可溶性分子的支架掺入驱动的，并且取决于共刺激分子的类型及其呈现的背景。在患有侵袭性淋巴瘤的小鼠中，在非治疗性 CAR-T 细胞给药后单次局部注射支架，可以产生更持久的记忆样 T 细胞，并延长动物的存活时间。具有优化配体呈递的可注射生物材料可能会提高 CAR-T 细胞疗法的治疗效果。