肿瘤细胞治疗研究
英文原题：Anti-tumor effects of GPC3 CAR-iNKT cells in murine models of hepatocellular carcinoma.
这些临床前研究结果表明，GPC3 CAR-iNKT细胞可能为HCC提供一种安全有效的治疗选择，值得在临床试验中进一步研究。
Glypican-3 (GPC3) 因其在肿瘤细胞上的选择性表达，已被确定为针对肝细胞癌 (HCC) 免疫治疗的一个有吸引力的靶点。嵌合抗原受体恒定自然杀伤T (CAR-iNKT) 细胞已成为CAR-T细胞的一种创新替代方案，为细胞治疗中的同种异体应用提供了潜在优势。在本研究中，我们构建了靶向GPC3的CAR-iNKT细胞，并在体外证明了它们对GPC3阳性HCC细胞的特异性细胞毒活性。利用小鼠HCC模型，我们进一步验证了GPC3 CAR-iNKT细胞能有效抑制肿瘤进展并提高生存结局。药代动力学研究显示CAR-iNKT细胞在体内具有良好的持久性，同时在关键器官中观察到的脱靶毒性较低。总体而言，这些临床前研究结果表明，GPC3 CAR-iNKT细胞可能为HCC提供一种安全有效的治疗选择，值得在临床试验中进一步研究。
Glypican-3 (GPC3) has been identified as a compelling target for immunotherapy against hepatocellular carcinoma (HCC), owing to its selective expression on tumor cells. Chimeric antigen receptor invariant natural killer T (CAR-iNKT) cells have emerged as an innovative alternative to CAR-T cells, offering potential advantages for allogeneic applications in cellular therapy. In this study, we engineered GPC3-targeted CAR-iNKT cells and demonstrated their specific cytotoxic activity against GPC3-positive HCC cells in vitro. Using a murine HCC model, we further validated that GPC3 CAR-iNKT cells effectively suppressed tumor progression and enhanced survival outcomes. Pharmacokinetic studies showed favorable persistence of CAR-iNKT cells in vivo, with low off-target toxicity observed in critical organs. Collectively, these preclinical findings suggest that GPC3 CAR-iNKT cells may provide a safe and effective therapeutic option for HCC, warranting further investigation in clinical trials.
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