肿瘤细胞治疗研究
英文原题：CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo.
CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo.
这些发现表明，DLL3-CAR NK-92 细胞可能是治疗 SCLC 的一种潜在策略。
小细胞肺癌（SCLC）具有高复发率、耐药性和治疗选择有限的特点。嵌合抗原受体（CAR）修饰的NK细胞是一种有前景的肿瘤免疫治疗方式。然而，其在SCLC中的潜在应用尚未被探索。Delta样配体3（DLL3）已被报道在SCLC中过表达，可能是CAR NK免疫治疗的合理靶点。在本研究中，我们开发了DLL3特异性NK-92细胞，并探索了其在SCLC治疗中的潜力。DLL3+ SCLC细胞系与DLL3-CAR NK-92细胞共培养表现出显著的体外细胞毒性和细胞因子产生。DLL3-CAR NK-92细胞在良好安全阈值下，在H446来源的肺转移肿瘤模型中诱导肿瘤消退。在SCLC皮下肿瘤模型中观察到DLL3-CAR NK-92细胞强效的抗肿瘤活性。此外，在DLL3+ SCLC异种移植瘤中检测到明显的肿瘤浸润DLL3-CAR NK-92细胞。这些发现表明，DLL3-CAR NK-92细胞可能是治疗SCLC的一种潜在策略。
Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta-like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3-specific NK-92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3 + SCLC cell lines with DLL3-CAR NK-92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3-CAR NK-92 cells induced tumor regression in an H446-derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3-CAR NK-92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor-infiltrated DLL3-CAR NK-92 cells were detected in DLL3 + SCLC xenografts. These findings indicate that DLL3-CAR NK-92 cells might be a potential strategy for the treatment of SCLC.
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