RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Lipid-based polymeric biomaterial-mediated ex vivo natural killer cell surface engineering.
Lipid-based polymeric biomaterial-mediated ex vivo natural killer cell surface engineering.
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自然杀伤(NK)细胞免疫疗法因其能够通过免疫突触形成选择性识别和消灭癌细胞,同时不伤害正常细胞而受到广泛关注。然而,NK细胞对实体瘤的治疗效果仍然有限,主要原因是肿瘤特异性靶向配体不足。尽管已开发出嵌合抗原受体(CAR)工程化NK细胞疗法来应对这一挑战,但其临床转化受到高成本、低转染效率以及与基因修饰相关的担忧等问题的阻碍。作为一种替代方案,基于生物材料的NK细胞表面工程已成为一种有前景的策略,可在不改变NK细胞固有特性的情况下增强肿瘤靶向能力。特别是,基于脂质的聚合物生物材料平台能够实现高效的配体-受体相互作用,从而增强NK细胞介导的肿瘤识别和细胞毒性。本综述重点介绍了基于脂质的NK细胞表面工程平台的最新进展,讨论了其相对于基因修饰的优势,以及其提高基于NK细胞的癌症免疫疗法疗效的潜力。
Natural killer (NK) cell-based immunotherapy has gained significant attention due to its ability to selectively recognize and eliminate cancer cells through immunological synapse formation while sparing normal cells.
However, the therapeutic efficacy of NK cells against solid tumors remains limited, primarily due to insufficient tumor-specific targeting ligands. Although chimeric antigen receptor (CAR)-engineered NK cell therapy has been developed to address this challenge, its clinical translation is hindered by challenges like high cost, low transfection efficiency, and concerns associated with genetic modification.
As an alternative, biomaterial-based NK cell surface engineering has emerged as a promising strategy to enhance tumor-targeting capabilities, without altering the intrinsic properties of NK cells. In particular, lipid-based polymeric biomaterial platforms enable efficient ligand-receptor interactions, thereby enhancing NK cell-mediated tumor recognition and cytotoxicity.
This review highlights recent advances in the lipid-based NK cell surface engineering platform, discussing its advantages over genetic modifications and its potential to improve the efficacy of NK cell-based cancer immunotherapy.
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