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目的利用热休克蛋白Hsp 70作为佐剂增强树突状细胞(DCs)递呈肿瘤抗原的能力并提高细胞毒T淋巴细胞(CTLs)对肺癌细胞的杀伤活性。方法外周血单个核细胞体外经GM-CSF和IL-4诱导产生树突状细胞,负载A549肺癌细胞裂解物的同时加入Hsp 70,诱导的自体CTLs用细胞毒试验和ELISA测定杀伤活性和细胞因子的分泌。同时建立荷瘤裸鼠模型,不同分组裸鼠一次或多次皮下注射CTLs。结果A 549冻融抗原+Hsp 70显著增强CTLs的增殖能力,诱导的CTLs对A 549细胞产生特异性杀伤并能抑制荷瘤裸鼠的肿瘤生长。结论DCs能有效呈递肺癌冻融抗原,诱导产生抗原特异性CTLs。在抗原致敏阶段加入Hsp 70能使CTLs杀伤活性进一步增强,提示Hsp 70在以DCs为基础的肺癌疫苗和过继免疫治疗中具有广阔前景。
Objective To enhance the ability of dendritic cells (DCs) to deliver tumor antigens by using heat shock protein Hsp 70 as an adjuvant and to enhance cytotoxic activity of cytotoxic T lymphocytes (CTLs) on lung cancer cells. Methods Peripheral blood mononuclear cells were induced by GM-CSF and IL-4 to produce dendritic cells in vitro. Hsp70 cells were loaded with A549 lung cancer cell lysate and the induced autologous CTLs were assayed for cytotoxicity and cytokines The secretion. At the same time, nude mice model was established. One or more subcutaneous injection of CTLs in different groups of nude mice. Results A 549 freeze-thaw antigen + Hsp 70 significantly enhanced the proliferation of CTLs. CTLs induced specific cytotoxicity on A 549 cells and inhibited the tumor growth of tumor-bearing nude mice. Conclusion DCs can effectively present lung cancer freeze-thaw antigen and induce the production of antigen-specific CTLs. The addition of Hsp 70 to the antigen-sensitized phase further enhanced the CTLs killing activity, suggesting that Hsp 70 has broad prospects for DCs-based lung cancer vaccine and adoptive immunotherapy.