DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation

Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micron-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR-T cells, driving local tumor clearance while sparing uninjected tumors in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to significantly impact human primary T cell activation phenotypes. This modular and versatile biomaterial ...生物材料可提升治疗制剂的安全性与呈递效能，助力实现高效免疫治疗；而对表面功能化的精准调控，是实现免疫细胞调控的核心前提。本研究开发了一类生物相容性免疫细胞结合颗粒（immune cell engaging particles, ICEp），该颗粒以合成短链DNA作为支架，可实现蛋白的高效负载与可调节性调控。为提升嵌合抗原受体（chimeric antigen receptor, CAR）T细胞疗法的安全性，我们通过瘤内注射微米级ICEp，为全身给药的与门型CAR-T细胞提供致敏信号。在免疫缺陷小鼠模型中，局部滞留的高密度致敏抗原呈递型ICEp可激活CAR-T细胞，实现局部肿瘤清除，同时避免未注射部位的肿瘤受到杀伤。研究表明，对共刺激配体（抗CD3与抗CD28抗体）的比例调控，以及ICEp表面细胞因子（白细胞介素-2, IL-2）的呈递方式，可显著影响人原代T细胞的激活表型。该模块化且通用性优异的生物材料体系……