免疫疗法
癌症免疫疗法
穿孔素
癌症研究
癌细胞
颗粒酶B
细胞毒性
癌症
转移
颗粒酶
自然杀伤细胞
化学
免疫系统
生物
免疫学
T细胞
体外
CD8型
生物化学
遗传学
作者
S. Kim,Shujin Li,M. Gajendiran,Ashok Kumar Jangid,Dong‐Joon Lee,Han‐Sung Jung,Kyobum Kim
标识
DOI:10.1016/j.cej.2023.145211
摘要
Current natural killer (NK) cell-based cancer immunotherapy for the treatment of solid tumors often exhibits insufficient cancer recognition specificity, thereby limiting therapeutic anticancer efficacy, especially for triple-negative breast cancers (TNBCs). In this study, we develop artificial lipid-folate conjugates, for stable anchoring onto NK cell surfaces via hydrophobic interactions, thus augmenting folate-mediated ligand-receptor immune interactions with target cancers. This hydrophobized conjugate anchor provides additional cancer recognition ligands without any sophisticated genetic modification, and successfully enhances the anticancer efficacies of surface-coated NK (SCNK) cells without disturbing their intrinsic properties. Augmented cancer recognition ability sequentially promotes the secretion of cytolytic granules (granzyme and perforin) with cytokine (TNF-α), demonstrating improved cytotoxicity of the SCNK cells. Furthermore, the SCNK cells significantly infiltrate into the tumor site, inducing tumor apoptosis/necrosis, and suppressing tumor progression and metastasis in TNBC mouse models. Taken together, our artificial lipid-folate conjugates enable the treatment of solid tumors by augmenting the cancer-recognition and tumor targeting capacity of surface-engineered NK cells.
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