肿瘤细胞治疗研究
英文原题：Surface-Engineered Natural Killer Cell-Derived Small Extracellular Vesicles Induce Potent Anti-Tumour Effects in Lung Cancer Cells.
我们的结果表明，装载 IL15 和西妥昔单抗的基因工程 NK-sEV 具有强效抗肿瘤活性和肿瘤靶向能力。
NK 细胞来源的小细胞外囊泡（sEV）具有内在抗肿瘤活性，并具备无细胞疗法的优势。本研究对 NK-sEV 进行基因工程改造，使其表达抗肿瘤细胞因子 IL-15，并在表面展示单克隆抗体 cetuximab，从而构建靶瘤能力增强的强效抗肿瘤免疫疗法。通过慢病毒改造生成携带 IL-15 和 cetuximab 的 NK-sEV（eEV）。体外实验中，eEV 选择性结合 EGFR⁺ 癌细胞，证实 cetuximab 介导的靶向作用。与对照 NK-sEV 相比，eEV 细胞毒性显著增强，既可直接诱导癌细胞死亡，也可促进 NK 细胞介导的杀伤。在肺癌小鼠模型中，eEV 选择性蓄积于肿瘤并显示显著抗肿瘤疗效。值得注意的是，单独给予 eEV 或与抗 PD-1 抗体联用，均有效抑制肿瘤生长。总体而言，携带 IL-15 和 cetuximab 的基因工程 NK-sEV 具有强效抗肿瘤活性和肿瘤靶向能力，提示 eEV 是癌症治疗的新型免疫疗法，具有显著潜力。
Small extracellular vesicles (sEVs) derived from natural killer (NK) cells possess inherent anti-tumour activity and offer the advantages of cell-free therapy. In this study, we genetically engineered NK-sEVs to express interleukin 15 (IL15), an anti-tumour cytokine, and the monoclonal antibody cetuximab on their surface, creating a potent anti-tumour immunotherapy with enhanced tumour-targeting capabilities. These IL15- and cetuximab-tethered NK-sEVs (eEVs) were generated using lentivirus-based modification. eEVs selectively bound to EGFR + cancer cells in vitro, confirming cetuximab-mediated targeting. Compared to control NK-sEVs, eEVs exhibited significantly enhanced cytotoxicity by directly inducing cancer cell death and promoting NK cell-mediated killing. In a lung cancer mouse model, eEVs selectively accumulated in tumours and exhibited significant anti-tumour efficacy. Notably, their administration, alone or in combination with anti-PD-1 antibody therapy, effectively suppressed tumour growth. Overall, our results indicate that genetically engineered NK-sEVs, equipped with IL15 and cetuximab, exhibit potent anti-tumour activity and tumour-targeting capabilities. These findings suggest that eEVs hold significant potential as a novel immunotherapeutic strategy for cancer treatment.
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