GPC3嵌合抗原受体（CAR）-NK细胞与Enoblituzumab联合使用可增强对肝细胞癌的抗肿瘤疗效
GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.
摘要(中文译文)
肝细胞癌（HCC）是全球癌症死亡的主要原因之一。尽管CAR-NK细胞疗法在血液系统恶性肿瘤中显示出前景，但其在HCC等实体瘤中的疗效往往因抗原逃逸而受限。在此，我们研究了一种双靶向策略，即将GPC3 CAR-NK细胞与B7H3阻断型单克隆抗体Enoblituzumab联合使用。我们通过数据库分析和流式细胞术证实了GPC3和B7H3在HCC组织和细胞系中的共表达。GPC3 CAR-NK细胞由扩增的人PBMC来源NK细胞制备。通过LDH释放实验和实时细胞分析评估体外对HCC细胞的细胞毒性，同时通过ELISA和流式细胞术检测IFN-γ分泌和CD107a脱颗粒。在荷皮下Huh7肿瘤的NCG小鼠中评估体内抗肿瘤疗效。GPC3和B7H3高共表达与患者不良预后相关。GPC3 CAR-NK细胞在体外对HCC细胞表现出强效细胞毒性。Enoblituzumab对B7H3阳性肿瘤触发了强效杀伤作用。值得注意的是，与任一单药治疗相比，联合治疗协同增强了细胞毒性、IFN-γ产生和CD107a脱颗粒。在体内，联合治疗显著抑制了肿瘤生长，且未引起体重下降或脾肿大，显示出良好的疗效和安全性。我们的研究结果表明，GPC3和B7H3双靶向可有效增强NK细胞介导的抗肿瘤活性。该策略同时利用了CAR介导的特异性和NK细胞内在机制，为开发双靶点免疫疗法以改善HCC患者预后提供了有力依据。
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Although CAR-NK cell therapies have shown promise in hematologic malignancies, their efficacy in solid tumors like HCC is often limited by antigen escape. Here, we investigated a dual-targeting strategy combining GPC3 CAR-NK cells with the B7H3-blocking monoclonal antibody Enoblituzumab. We confirmed GPC3 and B7H3 co-expression in HCC tissues and cell lines via database analysis and flow cytometry. GPC3 CAR-NK cells were generated from expanded human PBMC-derived NK cells. In vitro cytotoxicity against HCC cells was assessed by LDH release and real-time cell analysis, while IFN-γ secretion and CD107a degranulation were measured by ELISA and flow cytometry. In vivo antitumor efficacy was evaluated in NCG mice bearing subcutaneous Huh7 tumors. High GPC3 and B7H3 co-expression correlated with poor patient prognosis. GPC3 CAR-NK cells exhibited potent cytotoxicity against HCC cells in vitro. Enoblituzumab triggered strong killing effects against B7H3-positive tumors. Notably, the combination synergistically enhanced cytotoxicity, IFN-γ production, and CD107a degranulation compared to either monotherapy. In vivo, combination treatment significantly suppressed tumor growth without inducing weight loss or splenomegaly, demonstrating favorable efficacy and safety. Our findings demonstrate that dual targeting of GPC3 and B7H3 effectively enhances NK cell-mediated antitumor activity. This strategy leverages both CAR-mediated specificity and NK cell-intrinsic mechanisms, providing a strong rationale for developing dual-target immunotherapies to improve outcomes in HCC patients.
如何引用
AMA
Wen Zhuang, Guanyu Xiao, Mengyao Zhang, Jie Wang, Wenjing Tang, Yong Liang. GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154190.
APA
Wen Zhuang, Guanyu Xiao, Mengyao Zhang, Jie Wang, Wenjing Tang, Yong Liang (2026). GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154190
GB/T 7714
Wen Zhuang, Guanyu Xiao, Mengyao Zhang, Jie Wang, Wenjing Tang, Yong Liang. GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154190.
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