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:Promising approach for targeting ROBO1 with CAR NK cells to combat ovarian cancer primary tumor cells and organoids.
Promising approach for targeting ROBO1 with CAR NK cells to combat ovarian cancer primary tumor cells and organoids.
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本研究旨在探索使用外周血单核细胞(PBMC)来源的靶向ROBO1的嵌合抗原受体(CAR)NK细胞作为卵巢癌的个性化医学方法。
采用两步策略从卵巢癌患者的PBMC中生成靶向ROBO1的CAR NK细胞。使用xCELLigence RTCA、CCK-8和Live/Dead荧光测定法评估疗效。
与未进行ROBO1-CAR修饰的原代NK细胞相比,ROBO1-NK细胞在清除原代卵巢癌细胞和裂解卵巢肿瘤类器官方面表现出更高的效率。
这些发现凸显了从患者PBMC中开发靶向ROBO1的CAR-NK细胞作为卵巢癌个性化治疗选择的潜力。卵巢癌是一项严峻的临床挑战,迫切需要探索新的治疗方法。在本研究中,焦点指向ROBO1,这是一种已知在癌症血管生成和转移中发挥关键作用的分子,而在卵巢癌背景下研究有限。利用这一知识,我们试图利用来自患者自身的外周血单核细胞构建靶向ROBO1的嵌合抗原受体自然杀伤(CAR-NK)细胞。本研究的总体目标是利用自体资源的免疫治疗潜力,在临床环境中实现卵巢癌的个性化治疗策略。
Aim: This study aimed to explore using peripheral blood mononuclear cell (PBMC)-derived chimeric antigen receptor (CAR) NK cells targeting ROBO1 as a personalized medicine approach for ovarian cancer. Methods: A two-step strategy generated ROBO1-targeted CAR NK cells from PBMCs of ovarian cancer patients. Efficacy was evaluated using xCELLigence RTCA, CCK-8 and Live/Dead fluorescence assays. Results: ROBO1-NK cells exhibited higher efficiency in eradicating primary ovarian cancer cells and lysing ovarian tumor organoids compared with primary NK cells without ROBO1-CAR modification. Conclusion: These findings highlight the potential of developing ROBO1-targeted CAR-NK cells from patients' PBMCs as a personalized treatment option for ovarian cancer.
Ovarian cancer represents a formidable clinical challenge necessitating the urgent exploration of novel therapeutic approaches. In this study, the focus was directed toward ROBO1, a molecule known to play a pivotal role in cancer angiogenesis and metastasis, while limited investigation in the context of ovarian cancer.
Leveraging this knowledge, we sought to construct ROBO1-targeting chimeric antigen receptor natural killer (CAR-NK) cells utilizing peripheral blood mononuclear cells derived from the patients themselves. The overarching goal of this investigation was to harness the potential of immunotherapy using autologous resources to realize personalized treatment strategies for ovarian cancer in clinical settings.
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