树突状细胞疫苗治疗肺癌血源性转移的实验研究

THE EXPERIMENTAL MANAGEMENT BY DENDRITIC CELL VACCINES FOR HEMATOGENOUS METASTASIS OF LUNG CANCER

目的 探索应用树突状细胞肿瘤疫苗治疗肺癌血源性转移的可能性。方法 将Lewis肺癌细胞经尾静脉注射给C57BL/6J纯系小鼠建立肺癌血源性转移模型,应用树突状细胞负载合成的抗原多肽MUT-1,作为肿瘤疫苗进行免疫治疗。存活的小鼠再用10 倍数量的癌细胞皮下攻击,观察其免疫保护效应。这些小鼠的脾脏T淋巴细胞经纯化后进行体外抗原致敏,然后测定其特异性细胞毒效应。结果 尾静脉注射Lew is肺癌细胞可引起多脏器肿瘤播散,造成所有荷瘤小鼠死亡。但在注射Lewis肺癌细胞后24 h,用树突状细胞疫苗进行免疫治疗,可以完全控制转移病灶的形成及因肿瘤转移引起的死亡,这些小鼠对10 倍数量的Lew is 肺癌细胞再次攻击,具有显著的免疫保护作用。其脾脏T淋巴细胞对Lewis肺癌细胞具有特异性细胞毒效应。结论 树突状细胞疫苗治疗能够有效地清除血源性播散的肺癌细胞。

Objective To explore the feasibility of treatment with dendritic cell vaccines in lung cancer hematogenous metastasis.Methods The hematogenous metastasis model was established by venous injection of Lewis lung cancer cells in syngeneic C57BL/6J mice.The tumor bearing mice were treated by dendritic cells pulsed with an antigenic octapeptide (MUT 1)derived from this tumor.The surviving mice were challenged by subcutaneous injection of 10 fold amount of Lewis lung cancer cells.The splenic T lymphocytes of these mice were stimulated again with the vaccines in vitro and then tested for their specific cytotoxicity.Results The venous injection of Lewis lung cancer cells resulted in multiorganal metastases and death in the control mice without any treatment.In contrast,treatment with dendritic cell vaccine at 24 hr post injection completely inhibited tumor metastasis and rescued the tumor bearing mice from death.These mice developed a potent immune protection against the challenge with tumor cells at 10 fold amount.The T lymphocytes in the spleen of these mice showed a specific cytotoxicity against Lewis lung cancer cells in vitro.Conclusion The treatment with dendritic cell vaccine was potent in the control of lung cancer hematogenous metastasis.The underlying mechanism is the development of a potential cell mediated immune response specific for the tumor.$$$$