免疫治疗调节特异性抗原T细胞反应而非整个库有助于避免免疫相关的不良事件。我们开发了一种人工抗原呈递系统（aAPS），其中多个副本的多聚体肽-MHC-I复合物呈现小鼠限制性MHC-I的卵清蛋白衍生肽（信号1），以及共刺激配体（信号2）被化学连接到葡聚糖骨架上。当用这种aAPS处理对应的幼稚CD8+T细胞时，这些细胞经历了显著的扩增并展现出激活的表型。此外，效应细胞因子的升高表达导致这些细胞分化为细胞毒性T淋巴细胞，从而产生靶细胞溶解，表明aAPS的功能有效性。由于反复抗原刺激导致增殖潜力降低的CD8+T细胞也可以通过发展的aAPS重新扩张。因此，发展的aAPS有望进一步改进，用作快速定制的个性化免疫治疗药物，结合患者特定的MHC限制性肿瘤抗原和不同的共刺激信号，以调节肿瘤特异T细胞在癌症中的天然和抗原经历过程但筋疲力尽的情况。本文受版权保护。保留所有权利。

Immunotherapeutic modulation of antigen-specific T cell responses instead of the whole repertoire helps avoid immune-related adverse events. We have developed an artificial antigen-presenting system (aAPS) where multiple copies of a multimeric peptide-MHC class I complex presenting a murine class I MHC restricted ovalbumin-derived peptide (signal 1), along with a costimulatory ligand (signal 2) are chemically conjugated to a dextran backbone. Cognate naive CD8+ T cells, when treated with this aAPS underwent significant expansion and showed an activated phenotype. Furthermore, elevated expression of effector cytokines led to the differentiation of these cells to cytotoxic T lymphocytes which resulted in target cell lysis, indicative of the functional efficacy of the aAPS. CD8+ T cells with decreased proliferative potential due to repeated antigenic stimulation could also be re-expanded by the developed aAPS. Thus, the developed aAPS warrant further engineering for future application as a rapidly customizable personalized immunotherapeutic agent, incorporating patient-specific MHC-restricted tumor antigens and different costimulatory signals to modulate both naive and antigen-experienced but exhausted tumor-specific T cells in cancer. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.