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:Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy.
Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy.
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生物工程技术的快速发展引入了Fc融合蛋白,作为一种新型重组蛋白,其作为肿瘤治疗中颇具前景的生物制药产品。大量相关的抗肿瘤Fc融合蛋白已被研究,并处于不同的开发阶段。Fc融合蛋白是通过将抗体的Fc区与功能性蛋白或肽融合构建而成。它们保留了后者的生物活性以及前者的部分特性。这种结构和功能上的优势使Fc融合蛋白成为肿瘤免疫治疗中的有效工具,尤其是在自然杀伤(NK)细胞的招募和激活方面,NK细胞在肿瘤免疫治疗中发挥着关键作用。尽管肿瘤细胞已发展出规避NK细胞细胞毒性作用或诱导缺陷NK细胞的机制,Fc融合蛋白已被证明能够通过不同方式有效激活NK细胞以杀伤肿瘤细胞,例如抗体依赖性细胞介导的细胞毒性(ADCC),以不同方式激活NK细胞从而促进对肿瘤细胞的杀伤。在本综述中,我们聚焦于基于NK细胞的癌症免疫以及当前通过激活NK细胞进行抗肿瘤治疗的Fc融合蛋白的研究进展。
The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy.
Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.
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