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目的利用树突状细胞递呈肿瘤抗原的能力诱导出肿瘤特异性细胞毒性T淋巴细胞(CTL),用其治疗人肺腺癌细胞A549裸鼠移植瘤。方法外周血单个核细胞体外经粒细胞-巨噬细胞集落刺激因子(GM-CSF)和IL-4诱导产生树突状细胞,负载A549肺癌细胞裂解物诱导自体CTL,经细胞毒试验和ELISA测定CTL杀伤活性和细胞因子的分泌。同时制备荷瘤裸鼠模型,不同分组裸鼠一次或多次皮下注射CTL。结果A549冻融抗原能促进CTL增殖,可诱导产生CTL对A549细胞的特异杀伤,在效靶比为40∶1时杀伤率可达79.6%;一次接种后荷瘤裸鼠肿瘤生长减缓,多次接种肿瘤明显缩小且生存时间较对照组显著延长,具有明显的保护作用。结论树突状细胞能有效递呈肺癌冻融抗原,诱导产生具有一定治疗功效的抗肿瘤特异性CTL,提示临床应用以树突状细胞为基础的肺癌疫苗免疫治疗具有广阔前景。
Objective To induce tumor-specific cytotoxic T lymphocytes (CTLs) using the ability of dendritic cells to deliver tumor antigens and to treat human lung adenocarcinoma A549 xenografts in nude mice. Methods Peripheral blood mononuclear cells were induced by GM-CSF and IL-4 in vitro and dendritic cells were induced by loading A549 lung cancer cell lysate. Cytotoxicity assay and ELISA assay CTL killing activity and cytokine secretion. At the same time, nude mice bearing tumor model was prepared, and different groups of nude mice were injected with CTL subcutaneously once or several times. Results The freeze-thaw resistance of A549 could promote the proliferation of CTL and induce the specific cytotoxicity of CTL on A549 cells. The killing rate of A549 cells reached 79.6% when the effective target ratio was 40:1. The growth of tumor in nude mice was slowed down after multiple inoculation Inoculation tumor was significantly reduced and survival time significantly longer than the control group, with significant protective effect. Conclusions Dendritic cells can effectively deliver the freeze-thaw antigen of lung cancer and induce the production of anti-tumor-specific CTL with certain therapeutic efficacy. It is indicated that dendritic cell-based lung cancer vaccine immunotherapy has broad prospects.