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:Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.
Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.
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ErbB3在乳腺癌细胞中显著过表达,并与耐药和转移相关。此外,ErbB3表达水平与TIL(肿瘤浸润淋巴细胞)密度较低呈正相关,而后者是预后不良的标志。因此,ErbB3是癌症免疫治疗的有前景靶点。本文报告了靶向ErbB3的嵌合抗原受体(CAR)改造自然杀伤(NK)细胞的制备:采用VSV-G包膜假型慢病毒载体转导脐带血来源原代NK细胞。转导后的细胞稳定表达CAR,对ErbB3阳性乳腺癌细胞系的细胞毒作用增强。此外,在SK-BR-3异种移植小鼠模型中,抗ErbB3(aErbB3)CAR-NK细胞显著降低肿瘤负荷,且未见明显副作用。这些发现凸显了aErbB3 CAR-NK细胞作为ErbB3阳性乳腺癌靶向免疫疗法的潜力,并提示其可能成为传统治疗的有前景替代方案。
ErbB3 is markedly overexpressed in breast cancer cells and is associated with resistance and metastasis.
Additionally, ErbB3 expression levels are positively correlated with low densities of tumor-infiltrating lymphocytes, a marker of poor prognosis. Consequently, ErbB3 is a promising therapeutic target for cancer immunotherapy.
Here, we report the generation of ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) cells by transducing cord blood-derived primary NK cells using vsv-g envelope-pseudotyped lentiviral vectors. Transduced cells displayed stable CAR-expressing activity and increased cytotoxicity against ErbB3-positive breast cancer cell lines.
Furthermore, anti-ErbB3 (aErbB3) CAR-NK cells strongly reduced the tumor burden in the SK-BR-3 xenograft mouse model without observable side effects.
These findings underscore the potential of aErbB3 CAR-NK cells as targeted immunotherapy for ErbB3-positive breast cancer, suggesting a promising alternative to conventional treatments.
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