树突状细胞诱导抗胃癌作用体外实验研究

目的 :研究负载患者自体胃癌抗原后的树突状细胞 (DC)在体外诱导的特异性细胞毒性淋巴细胞 (CTL)对胃癌细胞的杀伤效应。方法 :以组合酶消化法从胃癌手术标本中获取胃癌细胞 ,冻融制备胃癌抗原。GM -CSF、IL - 4体外诱导外周血单个核细胞 (PBMC)获得DC并负载胃癌抗原 ,继而以其刺激自体T淋巴细胞制备胃癌抗原特异性CTL ;用CytoTox 96 TM检测CTL对患者自身胃癌细胞体外杀伤效应。结果 :负载胃癌抗原DC诱导的特异性CTL对患者自身胃癌细胞的杀伤率达 88 17% ,显著高于淋巴因子激活的杀伤细胞 (LAK)细胞的杀伤率 ,P <0 0 5。且其对同种不同分化类型的胃癌细胞株MGC80 3、MNK2 8也有较高的杀伤效应 ,而对LOVO及HepG2 肿瘤细胞无显著杀伤作用 ,P<0 0 1。结论 :负载胃癌抗原的DC体外可诱导出高效而特异的抗胃癌效应 ,揭示以DC为中心的肿瘤生物治疗可望提高胃癌综合治疗水平

Experiment study on the treatment of gastric cancer based on dendritic cells in vitro

Objective:To investigate the effect of specific cytotoxic T lymphocytes(CTLs)in vitro on gastric cancer.Methods:Combined enzyme digestion was employed to obtain gastric carcinoma cells from fresh specimens.These cells were frozen to produce carcinoma antigen.Granlocyte/macophage colony stimulating factor and interleukin 4 were used to induce peripheol blood mononuclear cell to get DC in vitro.Gastric carcinoma antigen specific CTL was generated from activated autologous T cell by lysate pulsed DCs.The cytotoxicity of CTL to patient's gastric carcinoma cell was detected by Cyto Tox96 TM in vitro.Different tumor cell lines and LAK cells were used as control in the experiment.Results: The killing rate of autologous gastric carcinoma cell by the antigen specific CTL reached at 88.17%,which was nearly twice as high as that of control.The CTL had much higher cytotoxicity to different differentiated types of gastric cancer cells such as MGC803 and MNK28,compared with LOVO and HepG2 tumor cells (P<0 01).Conclusion: DC might have potential value in clinical biotherapy of gastric cancer.