肿瘤细胞治疗研究
英文原题：Engineering Oncolytic Virus-Armed Macrophages for Enhanced Cancer Immunotherapy.
基于巨噬细胞的免疫疗法对实体瘤具有巨大前景，但由于免疫抑制性肿瘤微环境导致吞噬作用受损和M1型极化不稳定而受到限制。
基于巨噬细胞的免疫疗法对实体瘤具有巨大前景，但由于免疫抑制性肿瘤微环境导致吞噬功能受损和M1型极化不稳定而受到限制。在此，我们通过生物正交化学将负载溶瘤腺病毒（OA）的沸石咪唑酯骨架-8（ZIF-8）偶联到巨噬细胞表面，开发了工程化巨噬细胞（ZIFOA-M）。该平台利用局部病毒递送选择性下调肿瘤细胞上的“别吃我”信号（CD47和CD24），从而恢复巨噬细胞吞噬能力。此外，肿瘤内的病毒复制诱导免疫原性细胞死亡，释放主要损伤相关分子模式（DAMPs），维持M1型极化并促进持久抗肿瘤免疫。ZIFOA-M还增强肿瘤抗原呈递，引发强效的肿瘤特异性T细胞反应。我们的策略在单一局部平台中整合了吞噬功能恢复、微环境重塑和适应性免疫激活。ZIFOA-M为克服基于巨噬细胞的癌症免疫治疗中的关键障碍提供了一种互补且可转化的方法。
Macrophage-based immunotherapy holds great promise for solid tumors but is limited by impaired phagocytosis and unstable M1-type polarization due to immunosuppressive tumor microenvironments. Here, we develop engineered macrophages by conjugating oncolytic adenovirus (OA)-loaded zeolitic imidazolate framework-8 (ZIF-8) onto macrophage surfaces via bioorthogonal chemistry (ZIFOA-M). This platform leverages localized viral delivery to selectively downregulate "don't eat me" signals (CD47 and CD24) on tumor cells, thereby restoring macrophage phagocytic capacity. Moreover, viral replication within tumors induces immunogenic cell death, releasing major damage-associated molecular patterns (DAMPs) that sustain M1-type polarization and promote durable antitumor immunity. ZIFOA-M also enhances tumor antigen presentation, eliciting robust tumor-specific T cell responses. Our strategy integrates phagocytosis restoration, microenvironment remodeling, and adaptive immune activation in a single, localized platform. ZIFOA-M offers a complementary and translatable approach to overcome key barriers in macrophage-based cancer immunotherapy.
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