肿瘤细胞治疗研究
英文原题：Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer.
Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer.
分化型甲状腺癌（DTC）是甲状腺癌的主要类型，部分患者会出现复发、远处转移或难治，治疗选择有限。
分化型甲状腺癌（DTC）是最常见的甲状腺癌类型，部分患者会复发、发生远处转移或对治疗难治，治疗选择有限。嵌合抗原受体（CAR）修饰的自然杀伤（NK）细胞是可有效治疗多种耐药癌症的新型疗法。DTC 中促甲状腺激素受体（TSHR）的表达为 CAR 治疗提供了独特的肿瘤特异性靶点。本研究开发了一种创新策略，使用装载 TSHR 靶向 CAR 的改造 NK-92 细胞治疗 DTC。改造细胞对 TSHR 阳性 DTC 细胞系的细胞毒作用增强，并表现出脱颗粒和细胞因子释放增加。经照射后，细胞增殖能力被有效抑制，同时仍保持强效靶向杀伤能力。将照射处理后的细胞输注至携带 DTC 肿瘤的 NSG 小鼠体内，可显著抑制肿瘤。TSHR-CAR 改造 NK-92 细胞是推进 DTC 免疫治疗的一种有前景的现货型选择。
Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.
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