Abstract：
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.
摘要：
分化型甲状腺癌(DTC)是甲状腺癌的主要类型,一些患者复发，远处转移,或折射，揭示有限的治疗选择。嵌合抗原受体(CAR)修饰的自然杀伤(NK)细胞是有效对抗各种抗性癌症的革命性治疗剂。促甲状腺激素受体（TSHR）在DTC中的表达为CAR治疗提供了独特的肿瘤特异性靶标。这里,我们开发了一种使用改良NK-92细胞治疗DTC的创新策略,该细胞配备了TSHR靶向CAR.修饰的细胞对TSHR阳性DTC细胞系显示出增强的细胞毒性，并显示出升高的脱粒和细胞因子释放。接受辐照后，细胞有效地停止其增殖能力，同时保持有效的靶向杀伤能力。将这些辐射处理的细胞转移到具有DTC肿瘤的NSG小鼠中导致了深刻的肿瘤抑制。用TSHR-CAR修饰的NK-92细胞提供了一个有前途的，推进DTC免疫疗法的现成选择。
