肿瘤细胞治疗研究
英文原题：Pluripotent stem cell-derived chimeric antigen receptor-natural killer cells targeting epidermal growth factor receptor 2 for cancer immunotherapy.
嵌合抗原受体自然杀伤（CAR-NK）细胞正成为同种异体细胞免疫治疗的一个有前景的平台。
嵌合抗原受体自然杀伤（CAR-NK）细胞正成为一种有前景的异体细胞免疫治疗平台。在可用的细胞来源中，多能干细胞（PSC）来源NK细胞可持续补充并适合规模化生产，克服了原代NK细胞的局限。人表皮生长因子受体2（HER2）是一种在多种实体瘤中常过表达的膜蛋白，是有吸引力的癌症免疫治疗靶点。本研究设计了与绿色荧光蛋白（GFP）连接的抗HER2 CAR构建体，并通过慢病毒转导导入PSC。研究者建立了3个稳定PSC来源克隆（CAR-A、CAR-B和CAR-C），均共同表达抗HER2 CAR和GFP。在无异种成分、无饲养层培养条件下分化后，NK细胞中仍维持CAR表达。所得PSC来源CAR-NK细胞的表型和功能特征与野生型PSC来源NK细胞相近，但对HER2阳性癌细胞系的细胞毒性显著增强。这些发现显示，PSC来源抗HER2 CAR-NK细胞有望成为稳健且可规模化的免疫治疗方法。此外，该平台还可扩展用于生产靶向多种肿瘤相关抗原的CAR-NK细胞。
Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumorassociated antigens. [BMB Reports 2025; 58(11): 475-483].
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