肿瘤抗原脉冲致敏的树突状细胞疫苗抗肿瘤作用的实验研究

目的：进一步研究体外肿瘤抗原脉冲致敏的骨髓树突状细胞瘤苗主动免疫诱导小鼠体内抗肿瘤免疫应答，并观察其抵抗野生性肿瘤攻击的免疫保护作用及对荷瘤小鼠模型的免疫应答。方法：采用本室建立的骨髓树突状细胞分离与细胞因子体外扩增培养方法，并在体外经灭活ＮＳ１骨髓瘤细胞及其裂解产物脉冲刺激后直接作为疫苗，然后进行免疫预防与治疗的在体动物实验。结果：可从１只小鼠股骨中获得（３～５）×１０５个树突状细胞（ＤＣ），其纯度为９５％以上，对混合Ｔ淋巴细胞具有强刺激活性。主动免疫同系健康ＢＡＬＢ／Ｃ小鼠的试验显示，ＤＣ疫苗能诱导抗原特异的细胞毒性Ｔ淋巴细胞（ＣＴＬ）活性，免疫１次的动物首次受到肿瘤攻击后诱发肿瘤形成率为０％，再次攻击的肿瘤形成率为２０％；而免疫３次的动物两次攻击的肿瘤形成率皆为０％。主动免疫治疗同种荷瘤动物的试验表明，ＤＣ疫苗也能抑制肿瘤生长，荷瘤动物存活率提高及生存期明显延长。结论：肿瘤抗原体外致敏的树突状细胞能诱导宿主体内的抗肿瘤免疫保护性反应，且对荷瘤模型动物具有明显的免疫治疗作用。

An experimental study of in vivo induced antitumor immune reponses by vaccination of tumor lysate pulsed dendritic cells

Aims: In this study we developed another cancer vaccine based on deactivated tumor cells and lysate pulsed bone marrow generated dendritic cells (DC)and investigated whether the vaccine was capable of inducing antitumor immune responses in vivo.Methods: Using the isolation and expansion procedure established previously in our laboratory a large number of DCs were obtained,and pulsed in vitro with inactivated NS 1 myeloma cells and lysates,and then used as a cancer vaccine in the animal experiments.Results: Cultured DCs were potent stimulators in allogeneic mixed T lymphocyte reactions.After the pulsed DC vaccination of normal mice,these immunized animals were induced to develop more potent cytotoxic T lymphocytes (CTL) activity against stimulators targeted tumor cells,and obtained more effective immunoprotection from subsequent challenges of wild live NS 1 myeloma cells than those after vaccination directly with deactivated tumor cells.After active immunotherapy for the tumor bearing mice with the pulsed DC vaccine,the rate of their survival was increased and the survival time was greatly extended,and model tumor volumes were reduced or regressed.Conclusions:These results suggest that vaccination of normal and tumor bearing mice with the tumor lysate pulsed DCs could prime more potent antitumor immune response.It is concluded that the tumor antigen pulsed DC vaccine can enhance tumor immunogenicity and mediate tumor regession,indicating that it likely becomes a useful preparation for immunoprevention and immunotherapy of tumors.