第二代和第三代GPC3-CAR修饰的T淋巴细胞靶向杀伤肝细胞癌的体内研究
发布时间：2021-06-27 16:11
【背景和目的】嵌合抗原受体（Chimeric Antigen Receptors,CARs）是源自编码单链可变片段（scFv）的转基因的嵌合免疫球蛋白T细胞受体（TCR）分子,与T细胞的免疫受体酪氨酸活化基序相结合,能特异识别和结合肿瘤相关抗原的抗体,诱导细胞构象变化,导致转录因子表达和细胞因子释放,从而诱导T淋巴细胞产生针对肿瘤细胞的细胞毒活性。近年来,研究者们通过对CARs胞内信号区改造,旨在提高嵌合抗原分子传递信号的强度和持续时间,CAR-T已经历了从第一代到第五代的变迁,成为了肿瘤免疫治疗的新热点。肝细胞癌（Hepatocellular Carcinoma,HCC）是世界上最常见的癌症之一,尽管HCC现阶段的临床治疗水平有了极大提高,但死亡率并无明显改善,5年以上生存率低至25%39%左右。磷脂酰肌醇蛋白聚糖-3（Glypican-3,GPC3）是磷脂酰肌醇蛋白聚糖家族的成员之一,据报道该蛋白在原发性肝细胞癌中表达率高达80%,但在正常肝组织、肝硬化组织或癌旁组织中不表达。由于GPC3对肝细胞癌的诊断具有特异性强和敏感性高的优势,GPC3有望成为诊断和治疗...
【文章来源】：福建医科大学福建省
【文章页数】：66 页
【学位级别】：硕士
【部分图文】：
2SK-Hep-1荷瘤小鼠体重Figure2.2.2WeightofSK-Hep-1groups
图 2.3.1 HepG2 组荷瘤小鼠体内过继免疫治疗前后小鼠荷瘤的变化Figure2.3.1 Changes of HepG2 xenografts treated with the indicated T cells or salin表 1 HepG2 组的肿瘤体积变化（单位：mm3）（均数±标准差）G2 Saline Mock GBBz G28BBz118.32±7.26123.74±9.22146.25±21.18195.58±37.62244.39±30.33290.21±20.50464.26±42.83606.87±89.55819.83±62.02135.63±7.87139.91±9.04166.97±13.12205.96±26.84230.46±30.94255.18±45.55335.29±105.51371.62±127.93454.10±127.16127.26±13.21131.01±12.71131.00±12.68132.82±16.41137.19±18.01135.52±15.30137.44±15.27133.76±22.86131.83±24.16109.74±10.117.00±11.114.05±13.104.95±12.94.92±13.355.18±11.154.97±12.134.08±6.8827.90±2.8913579111315
图 2.3.3 SK-Hep-1 组荷瘤小鼠体内过继免疫治疗前后小鼠荷瘤的变化Figure2.3.3 Changes of Sk-Hep-1xenografts treated with the indicated T cells or saline表 2 SK-Hep-1 组的肿瘤体积变化（单位：mm3）（均数±标准差） Saline Mock GBBz G28BBze 103.36±8.03111.75±8.10123.43±26.78119.10±14.00146.42±26.32180.72±28.05206.13±29.54232.20±35.88266.91±41.54100.53±11.92103.65±12.19106.61±13.39111.03±11.25123.05±12.27132.57±12.37145.38±14.48163.79±15.27198.03±18.14100.27±9.25103.99±8.59112.13±10.07111.08±8.01124.08±10.53129.44±10.89138.75±9.44160.76±13.50199.37±16.1393.25±10.7499.92±9.26107.62±15.69102.25±16.72109.49±15.96119.74±19.01133.01±14.25155.37±14.73188.98±21.95ay1ay3ay5ay7ay9ay11ay13ay15
本文编号：3253173
【文章来源】：福建医科大学福建省
【文章页数】：66 页
【学位级别】：硕士
【部分图文】：
2SK-Hep-1荷瘤小鼠体重Figure2.2.2WeightofSK-Hep-1groups
图 2.3.1 HepG2 组荷瘤小鼠体内过继免疫治疗前后小鼠荷瘤的变化Figure2.3.1 Changes of HepG2 xenografts treated with the indicated T cells or salin表 1 HepG2 组的肿瘤体积变化（单位：mm3）（均数±标准差）G2 Saline Mock GBBz G28BBz118.32±7.26123.74±9.22146.25±21.18195.58±37.62244.39±30.33290.21±20.50464.26±42.83606.87±89.55819.83±62.02135.63±7.87139.91±9.04166.97±13.12205.96±26.84230.46±30.94255.18±45.55335.29±105.51371.62±127.93454.10±127.16127.26±13.21131.01±12.71131.00±12.68132.82±16.41137.19±18.01135.52±15.30137.44±15.27133.76±22.86131.83±24.16109.74±10.117.00±11.114.05±13.104.95±12.94.92±13.355.18±11.154.97±12.134.08±6.8827.90±2.8913579111315
图 2.3.3 SK-Hep-1 组荷瘤小鼠体内过继免疫治疗前后小鼠荷瘤的变化Figure2.3.3 Changes of Sk-Hep-1xenografts treated with the indicated T cells or saline表 2 SK-Hep-1 组的肿瘤体积变化（单位：mm3）（均数±标准差） Saline Mock GBBz G28BBze 103.36±8.03111.75±8.10123.43±26.78119.10±14.00146.42±26.32180.72±28.05206.13±29.54232.20±35.88266.91±41.54100.53±11.92103.65±12.19106.61±13.39111.03±11.25123.05±12.27132.57±12.37145.38±14.48163.79±15.27198.03±18.14100.27±9.25103.99±8.59112.13±10.07111.08±8.01124.08±10.53129.44±10.89138.75±9.44160.76±13.50199.37±16.1393.25±10.7499.92±9.26107.62±15.69102.25±16.72109.49±15.96119.74±19.01133.01±14.25155.37±14.73188.98±21.95ay1ay3ay5ay7ay9ay11ay13ay15
本文编号：3253173
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