细胞毒T淋巴细胞识别人肾癌c-erbB-2蛋白

c-erbB-2 protein of human renal cell carcinoma can be recognized by cytotoxic T lymphocytes

目的 为肾癌特异性免疫治疗提供实验依据。 方法 采用流式细胞仪和RT PCR方法检测人肾癌细胞系c erbB 2和HLA A2分子的表达。肿瘤细胞裂解物 (Tuly)负载树突状细胞 (DCs)体外诱导肾癌患者自体外周血单个核细胞产生特异的细胞毒T细胞 (CTL)。采用CTLs杀伤表达或不表达c erbB 2和HLA A2的肾癌细胞。采用抗体封闭试验证实c erbB 2的免疫原性。 结果 c erbB 2是肾癌肿瘤相关抗原。负载Tuly的DCs(DC Tuly)诱导的CTLs特异性高杀伤c erbB 2 + HLA A2 + 肾癌细胞 ,但非特异性低杀伤c erbB 2 - 或HLA A2 - 肾癌细胞。此特异性杀伤作用能被抗c erbB 2和抗CD8单克隆抗体封闭。 结论 c erbB 2 + 和HLA A2 + 的肾癌患者采用过继性细胞免疫治疗可能会提高疗效。

ObjectiveTo provide experimental proof for the specific immunotherapy in patients with renal cell carcinoma (RCC).MethodsThe expression of c-erbB-2 and HLA-A2 molecules in RCC were examined by flow cytometery and HLA-A2 cDNA RT-PCR.Tumor lysatic antigens (Tuly) was used to load DCs (DC-Tuly) to induce the generation of c-erbB-2 specific CTLs derived from peripheral blood mononuclear cells of RCC patients in vitro and CTLs was used to kill RCC cells which express or not express c-erbB-2 and HLA-A2.The cytotoxic activity of induced CTLs was further studied by antibodies (anti-c-erbB-2 and anti-CD 8) blocking assay.Resultsc-erbB-2 protein is tumor associated antigens for RCC.DC-Tuly induced specific CTLs highly killed c-erbB-2+ HLA-A2+ autologous and allogenic RCC,but non-specific ones lowly killed c-erbB-2- HLA-A2+ or c-erbB-2+ HLA-A2-RCC cells. The cytotoxic activity against tumor cells was blocked by anti-c-erbB-2 and anti-CD 8 monoclonal antibodies.ConclusionsThese results suggest that this specific CTLs adoptive immunotherapy for RCC patients with c-erbB-2+ HLA-A2+ could be a novel approach for clinical use.