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Development of GPC3-CAR-NK cells and optimization as a therapy for HCC
Cao, Bihui; Ni, Qianqian; Chen, Zhuxin; Yang, Shuo; Zhang, Xinkui; Su, Haotao; Zheng, Zhenfeng; Zhao, Qi; Zhu, Xiaolan; Liu, Manting
2024-06-26
Source PublicationJournal of leukocyte biology
ISSN1938-3673
Volume0Issue:0Pages:1-11
AbstractHepatocellular carcinoma (HCC) is a highly malignant tumor characterized by insidious onset and rapid progression, with limited treatment choices. One treatment modality, chimeric antigen receptor (CAR)-modified natural killer (NK) cell immunotherapy, has shown promise for various cancers. In this study, we developed two GPC3-specific CAR-NK-92 cell lines (GPC3-CAR-NK) and explored their antitumor efficacy for the treatment of HCC. Significant levels of cytokine production and in vitro cytotoxicity were produced following co-culture of GPC3+ HCC cells with the developed GPC3-CAR-NK cells. GC33-G2D-NK cells with NK cell-specific signaling domains showed better activation and killing abilities than GC33-CD28-NK cells containing T cell-specific signaling domains. Moreover, GC33-G2D-NK cells efficiently eliminated tumors in cell-derived xenograft and patient-derived xenograft mouse models. In an abdominal metastasis model, intraperitoneally delivered GC33-G2D-NK cells showed better antitumor ability than intravenously injected cells. Finally, the combination of microwave ablation with GC33-G2D-NK cell administration showed greater CAR-NK infiltration and tumor regression in ablated tumors than monotherapy alone. These findings indicate that administration of GPC3-CAR-NK cells may be a potential strategy for the treatment of HCC, and regional delivery or their combination with microwave ablation may optimize their efficacy against HCC and may have translational value.
KeywordHcc Mwa Chimeric Antigen Receptor Glypican-3 Natural Killer.
DOI10.1093/jleuko/qiae144
URLView the original
Indexed BySCIE
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Document TypeJournal article
CollectionDEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorZhao, Qi; Zhu, Xiaolan; Liu, Manting
AffiliationMoE Frontiers Science Center for Precision Oncology, Faculty of Health Sciences, University of Macau, Macau SAR, China
Recommended Citation
GB/T 7714
Cao, Bihui,Ni, Qianqian,Chen, Zhuxin,et al. Development of GPC3-CAR-NK cells and optimization as a therapy for HCC[J]. Journal of leukocyte biology, 2024, 0(0), 1-11.
APA Cao, Bihui., Ni, Qianqian., Chen, Zhuxin., Yang, Shuo., Zhang, Xinkui., Su, Haotao., Zheng, Zhenfeng., Zhao, Qi., Zhu, Xiaolan., & Liu, Manting (2024). Development of GPC3-CAR-NK cells and optimization as a therapy for HCC. Journal of leukocyte biology, 0(0), 1-11.
MLA Cao, Bihui,et al."Development of GPC3-CAR-NK cells and optimization as a therapy for HCC".Journal of leukocyte biology 0.0(2024):1-11.
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