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:Natural killer cell engagers for cancer immunotherapy.
Natural killer cell engagers for cancer immunotherapy.
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这篇综述文章探讨了双特异性、三特异性和多特异性NK细胞衔接器(NKCEs)这一快速发展的领域,强调其作为癌症免疫治疗前沿方法的潜力。NKCEs通过增强抗体依赖性细胞介导的细胞毒性(ADCC),较传统单克隆抗体(mAbs)具有显著进步。其实现方式是与NK细胞活化受体和肿瘤相关抗原(TAAs)稳定且选择性地结合。与依赖其Fc段与CD16a之间相对短暂相互作用的传统mAbs不同,NKCEs与NK细胞上的一系列活化受体(如CD16a、NKG2D、NKp30、NKp46、NKG2C)和抑制性受体(如Siglec-7)建立更稳固的连接,从而提高癌细胞杀伤效能和特异性。这篇综述文章批判性地审视了用于癌症免疫治疗的双特异性、三特异性和多特异性NKCEs的工程化策略,深入分析了制药和生物技术公司目前正在开发的NKCE平台技术的最新进展,并讨论了这些产品的临床前和临床进展。尽管NKCEs展现出巨大前景,但本综述强调仍需持续研究以优化其治疗效能,并克服与癌症患者中NK细胞功能相关的障碍。最终,本文概述了基于NKCE的癌症免疫治疗的当前格局和未来前景,强调其革新癌症治疗的潜力。
This review article explores the rapidly evolving field of bi-, tri-, and multi-specific NK cell engagers (NKCEs), highlighting their potential as a cutting-edge approach in cancer immunotherapy. NKCEs offer a significant advancement over conventional monoclonal antibodies (mAbs) by enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). They achieve this by stably and selectively binding to both NK cell activating receptors and tumor-associated antigens (TAAs). Unlike traditional mAbs, which depend on the relatively transient interaction between their Fc region and CD16a, NKCEs establish more robust connections with a range of activating receptors (e. g. , CD16a, NKG2D, NKp30, NKp46, NKG2C) and inhibitory receptors (e. g. , Siglec-7) on NK cells, thereby increasing cancer cell killing efficacy and specificity.
This review article critically examines the strategies for engineering bi-, tri-, and multi-specific NKCEs for cancer immunotherapy, providing an in-depth analysis of the latest advancements in NKCE platform technologies currently under development by pharmaceutical and biotech companies and discussing the preclinical and clinical progress of these products.
While NKCEs show great promise, the review underscores the need for continued research to optimize their therapeutic efficacy and to overcome obstacles related to NK cell functionality in cancer patients. Ultimately, this article presents an overview of the current landscape and future prospects of NKCE-based cancer immunotherapy, emphasizing its potential to revolutionize cancer treatment.
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