工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.
Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.
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T细胞浸润不足严重损害了过继性细胞疗法(ACT)对实体瘤的抗肿瘤疗效。在此,我们提出一种简便的免疫细胞表面工程策略,旨在通过快速鉴定肿瘤特异性结合配体并改善输注细胞向实体瘤的浸润,从而大幅增强Th9介导的ACT的抗肿瘤疗效。利用从噬菌体展示中筛选出的肿瘤靶向肽对Th9细胞进行非基因修饰,不仅实现了针对高度异质性实体瘤的精准靶向ACT,还显著增强了CD8+ T细胞的浸润,从而改善了抗肿瘤效果。在机制上,输注经肿瘤特异性结合配体修饰的Th9细胞促进了杀瘤细胞的分布增强,并通过IL-9介导的免疫调节重塑了实体瘤的免疫抑制微环境。总体而言,我们提出了一种简单、经济且对细胞友好的策略,以增强ACT对实体瘤的疗效,并具有补充当前ACT的潜力。
Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors.
Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8 + T cells, which led to improved antitumor outcomes.
Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.
Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.
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