间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Dendritic Cell Vaccine Loaded with MG-7 Antigen Induces Cytotoxic T Lymphocyte Responses against Gastric Cancer.
Dendritic Cell Vaccine Loaded with MG-7 Antigen Induces Cytotoxic T Lymphocyte Responses against Gastric Cancer.
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树突状细胞(DC)是能够激活T细胞并启动初次免疫应答的抗原提呈细胞。个体化DC疫苗在一些临床初步研究中显示出一定的抗肿瘤潜力。
然而,这些疫苗难以制备且抗肿瘤应答有限。在本研究中,开发了一种具有高抗肿瘤应答的慢病毒载体编程DC疫苗。通过慢病毒载体转染,DC疫苗负载MG-7抗原(MG-7Ag)。使用三种代表性胃癌细胞系,如KATO-3、MKN45和SNU16,评估MG-7Ag DC疫苗的体外细胞毒性效应。
此外,我们在患者来源异种移植(PDX)小鼠模型中检测了由MG-7Ag DC疫苗诱导的特异性细胞毒性T淋巴细胞(CTL)的体内抗肿瘤疗效。当前数据表明,MG-7Ag DC疫苗诱导了强效的CTL活性。这些CTL对MG-7高表达的KATO-3和MKN45均具有显著细胞毒性效应。
此外,MG-7Ag DC疫苗介导的CTL显著抑制裸鼠中肿瘤异种移植物的生长。MG-7Ag DC疫苗激活淋巴细胞的细胞毒性效应,可作为胃癌免疫治疗中的疫苗使用。
Dendritic cells (DCs) are antigen-presenting cells that can activate T cells and initiate a primary immune response. Personalized DC vaccines have demonstrated a modest antitumor potential in some clinical pilot studies.
However, those vaccines are difficult to manufacture and have a limited antitumor response. In this study, a lentiviral vector-programmed DC vaccine with high antitumor responses is developed. By transfecting with a lentiviral vector, the DC vaccine is loaded with MG-7 antigen (MG-7Ag). Three representative gastric cancer cell lines, such as KATO-3, MKN45, and SNU16, are used to estimate the in vitro cytotoxic effect of the MG-7Ag DC vaccine.
Furthermore, we examine the in vivo antitumor efficacy of specific cytotoxic T lymphocytes (CTLs) induced by the MG-7Ag DC vaccine in patient-derived xenograft (PDX) mice models. The current data demonstrate that the MG-7Ag DC vaccine induced a potent CTL activity. Those CTLs have a significant cytotoxic effect on both KATO-3 and MKN45 with high level of MG-7 expression.
In addition, MG-7Ag DC vaccine-mediated CTLs significantly inhibit the growth of tumor xenografts in nude mice. The MG-7Ag DC vaccine activate the cytotoxic effect of lymphocytes and can be employed as a vaccine in gastric cancer immunotherapy.
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