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:Scalable process development of NK and CAR-NK expansion in a closed bioreactor.
Scalable process development of NK and CAR-NK expansion in a closed bioreactor.
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生产大量功能性NK和CAR-NK细胞是NK免疫治疗的瓶颈之一。在本研究中,我们利用依赖透气膜技术的G-Rex 100M生物反应器,开发了一种大规模、可靠且可行的NK和CAR-NK生产方法。该系统可容纳大量培养基并增强氧气输送,为癌症治疗所需的大规模PBNK和CAR-NK扩增创造了有利条件。在这些生物反应器中扩增的外周血NK细胞(PBNKs)和CAR-NK细胞保留了相似的免疫表型,并对肝细胞癌(HCC)细胞表现出与在G-Rex 6孔生物反应器中扩增的NK和CAR-NK细胞相当的细胞毒性。重要的是,冷冻保存对使用G-Rex 100M生物反应器扩增的NK细胞的细胞毒性影响极小,建立了一个稳健的NK和CAR-NK细胞规模化生产平台。该方法有望推动“现货型”NK细胞的开发,支持NK细胞免疫治疗未来的临床实施。
Production of large amounts of functional NK and CAR-NK cells represents one of the bottlenecks for NK-based immunotherapy. In this study, we developed a large-scale, reliable, and practicable NK and CAR-NK production using G-Rex 100M bioreactors, which depend on a gas-permeable membrane technology.
This system holds large volumes of medium with enhanced oxygen delivery, creating conditions conducive to large-scale PBNK and CAR-NK expansions for cancer therapy. Both peripheral blood NK cells (PBNKs) and CAR-NKs expanded in these bioreactors retained similar immunophenotypes and exhibited comparable cytotoxicity towards hepatocellular carcinoma (HCC) cells akin to that of NK and CAR-NK cells expanded in G-Rex 6 well bioreactors.
Importantly, cryopreservation minimally affected the cytotoxicity of NK cells expanded using the G-Rex 100M bioreactors, establishing a robust platform for scaled-up NK and CAR-NK cell production. This method is promising for the development of "off-the-shelf" NK cells, supporting the future clinical implementation of NK cell immunotherapy.
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