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.
肿瘤细胞治疗研究
英文原题:From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.
From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.
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免疫细胞衔接器已成为一类强大的多特异性治疗药物,能够将免疫效应细胞重定向至肿瘤细胞,从而诱导靶向细胞毒性。其中,T 细胞衔接器(TCEs)代表了临床进展最为先进的平台,多种已获批药物在血液系统恶性肿瘤中展现出显著疗效。然而,其更广泛的应用仍受限于全身性毒性、抗原异质性以及在实体瘤中疗效降低等问题。为应对这些挑战,下一代 TCEs 正通过工程化改造以提升选择性并优化信号传导特性。与此同时,越来越多的关注转向衔接其他免疫效应细胞,包括 γδ T 细胞、NK 细胞和髓系细胞群体,这些细胞提供了互补的肿瘤识别和免疫调节机制。在本综述中,我们总结了 T 细胞或其他免疫细胞衔接器背后的生物学原理,重点介绍了新兴的替代平台,并讨论了正在塑造可编程癌症免疫治疗未来的不断演进的工程化策略。
Immune cell engagers have emerged as a powerful class of multi-specific therapeutics that redirect immune effector cells toward tumor cells to induce targeted cytotoxicity. Among these, T cell engagers (TCEs) represent the most clinically advanced platform, with multiple approved agents demonstrating substantial efficacy in hematologic malignancies.
However, their broader application remains limited by systemic toxicities, antigen heterogeneity, and reduced efficacy in solid tumors. To address these challenges, next-generation TCEs are being engineered with improved selectivity, and optimized signaling properties.
In parallel, increasing attention has shifted toward engaging alternative immune effectors, including γδ T cells, natural killer cells, and myeloid populations, which provide complementary mechanisms of tumor recognition and immune modulation. In this Review, we summarize the biological principles underlying T or other immune cell engagers, highlight emerging alternative platforms, and discuss evolving engineering strategies that are shaping the future of programmable cancer immunotherapy.
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