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:Synergistic Chemo-Immunotherapy: Recombinant Fusion Protein-Based Surface Modification of NK Cell for Targeted Cancer Treatment.
Synergistic Chemo-Immunotherapy: Recombinant Fusion Protein-Based Surface Modification of NK Cell for Targeted Cancer Treatment.
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尽管传统的联合抗癌治疗已显示出令人鼓舞的结果,但开发创新方法以增强和整合化疗与免疫治疗仍存在显著的研究兴趣。本研究介绍了一种基于重组融合蛋白的细胞表面修饰系统,该系统将化疗和免疫治疗协同结合为单一靶向的化学-免疫治疗方法。一种由抗体特异性结合结构域和细胞穿透结构域组成的细胞表面修饰蛋白,通过结合免疫细胞表面的抗体,快速将免疫细胞转化为化学-免疫治疗剂。利用一种非侵入性、无毒、无需化学修饰和结合的方法,我们的系统通过瞬时将靶向细胞毒性药物引入免疫细胞内,均一地转化免疫细胞。负载抗体-药物偶联物(ADCs)的表面工程化免疫细胞显著抑制靶肿瘤的生长,并增强对癌细胞的靶向清除。
因此,通过细胞表面修饰蛋白修饰以整合ADCs的NK细胞,有望实现靶向识别癌细胞、化疗和免疫治疗的联合效应,从而增强其抗癌治疗效果。该策略允许高效快速地制备先进的化学-免疫治疗剂以治疗多种类型的癌症,并为提高癌症治疗疗效提供了巨大的潜力。
While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy.
This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells.
Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody-drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells.
Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment.
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