嵌合抗原受体（CAR）-T细胞免疫疗法已被批准用于治疗血液恶性肿瘤，但由于瘤内CAR-T细胞浸润不足，在实体瘤治疗中仍远未令人满意。在此，一种可注射的超分子水凝胶系统，基于与靶向抗CD3e f(ab')2片段的T细胞和α-环糊精(α-CD)缀合的阳离子聚合物mPEG-PCL-PEI (PPP)之间的自组装，具有设计用于加载带有T细胞特异性CD2启动子的质粒CAR（pCAR），在人源化小鼠模型中成功实现了CAR-T细胞在肿瘤部位的原位制造和有效积累。更重要的是，由于这种肿瘤微环境重编程，显着促进了细胞炎症细胞因子（IL-2、TNF-α和IFN-γ）或肿瘤杀伤蛋白颗粒酶B的分泌，从而逆转了免疫抑制微环境并显着增强了细胞内的免疫抑制能力。肿瘤CAR-T细胞和细胞毒性T细胞浸润。据我们所知，这是使用可注射超分子水凝胶对 CAR-T 细胞进行原位重编程的开创性报告，这可能有益于实体瘤 CAR-T 免疫治疗。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

Chimeric antigen receptor (CAR)-T cell immunotherapy has been approved in the treatment of hematological malignancies, but remains far from satisfaction in solid tumor treatment due to inadequate intra-tumor CAR-T cell infiltration. Herein, an injectable supramolecular hydrogel system, based on self-assembly between cationic polymer mPEG-PCL-PEI (PPP) conjugated with T cell targeting anti-CD3e f(ab')2 fragment and α-cyclodextrin (α-CD), has been designed to load plasmid CAR (pCAR) with T cell specific CD2 promoter, which successfully achieved in situ fabrication and effective accumulation of CAR-T cells at the tumor site in humanized mice models. More importantly, due to this tumor microenvironment reprogramming, secretion of cellular inflammatory cytokines (IL-2, TNF-α, and IFN-γ) or tumor killer protein granzyme B was significantly promoted, which reversed the immunosuppressive microenvironment and significantly enhanced the intra-tumor CAR-T cells and cytotoxic T cells infiltration. To the best of our knowledge, this is a pioneer report of using injectable supramolecular hydrogel for in situ reprogramming CAR-T cells, which might be beneficial for solid tumor CAR-T immunotherapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.