再分化使能的 TSHRCART 细胞克服侵袭性甲状腺癌中的抗原丢失
Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.
这些发现确立了肿瘤再分化作为一种可推广的策略,用于克服抗原丢失并增强CART细胞疗法在甲状腺癌以及可能其他实体瘤中的疗效。
英文原题:Genetically Engineered Cell Membrane-Coated Nanodrug for Targeted Treatment of Thyroid Cancer.
甲状腺癌是最常见的内分泌恶性肿瘤,尤其是在放射性碘难治性分化型甲状腺癌(RAIR-DTC)患者中,其治疗选择有限且临床预后较差。
甲状腺癌是最常见的内分泌恶性肿瘤,尤其是放射性碘难治性分化型甲状腺癌(RAIR-DTC)患者,其治疗选择有限且临床预后较差。本研究将多柔比星和索拉非尼负载于光热转换剂介孔聚多巴胺中,形成mPDS。通过肿瘤细胞膜包覆工程形成mPDS@CAR-M,显著提高了肿瘤靶向性。被肿瘤细胞内吞后,所载药物在近红外激光照射下迅速释放。mPDS@CAR-M通过增强氧化应激、抑制PI3K-AKT-mTOR信号通路并诱导细胞毒性自噬,有效抑制肿瘤细胞增殖。通过激活有害自噬,mPDS@CAR-M进一步抑制上皮-间充质转化过程,降低肿瘤细胞迁移能力。体内实验表明,mPDS@CAR-M显著缩小肿瘤体积,其治疗效果与靶向表面抗原的表达水平密切相关。因此,mPDS@CAR-M在RAIR-DTC治疗中展现出显著潜力,为进一步临床探索提供了新方向。
Thyroid cancer is the most common endocrine malignancy, particularly in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC), who have limited treatment options and poor clinical prognosis. In this study, doxorubicin and sorafenib were loaded into the photothermal conversion agent mesoporous polydopamine, forming mPDS. Tumor cell membrane coating engineering resulted in the formation of mPDS@CAR-M, significantly improving tumor targeting. After internalization by tumor cells, the loaded drugs are rapidly released under near-infrared laser irradiation. mPDS@CAR-M effectively inhibits tumor cell proliferation by enhancing oxidative stress, suppressing the PI3K-AKT-mTOR signaling pathway, and inducing cytotoxic autophagy. By activating harmful autophagy, mPDS@CAR-M further inhibits the epithelial-mesenchymal transition process, reducing tumor cell migration capacity. In vivo experiments showed that mPDS@CAR-M significantly reduced tumor volume, with its therapeutic efficacy closely related to the expression level of the targeted surface antigen. Therefore, mPDS@CAR-M demonstrates significant potential in the treatment of RAIR-DTC, providing a novel direction for further clinical exploration.
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