骨髓树突状细胞融合瘤苗抗肿瘤免疫预防与治疗的实验研究

目的：进一步研究树突状细胞与肿瘤细胞的融合瘤苗细胞主动免疫诱导体内抗肿瘤免疫反应及对荷瘤小鼠的免疫治疗效果。方法：直接分离骨髓树突状细胞和体外生长因子诱导扩增培养相结合，获得大量高纯度的树突状细胞，再以５００ｇ／ＬＰＥＧ诱导其与ＮＳ１骨髓细胞融合，ＨＡＴ选择培养得到两者的融合细胞，体外进行混合淋巴细胞培养，并进行免疫预防与治疗的在体动物实验。结果：融合细胞也能诱导淋巴细胞的增殖反应，而ＮＳ１无此作用。体内免疫预防试验表明，融合细胞活瘤苗１次免疫后，诱导出较强的细胞毒性Ｔ淋巴细胞（ＣＴＬ），并获得抵抗野生型ＮＳ１攻击的保护性反应，但对无关瘤株则无此抵抗力。融合细胞对荷瘤小鼠的免疫治疗试验显示，融合细胞静脉注射后，能够明显抑制肿瘤生长，延长其生存期。结论：树突状细胞与肿瘤细胞融合后的瘤苗体内免疫，能有效地诱导抗肿瘤免疫反应，可望成为肿瘤免疫预防和免疫治疗的新途径。

Induced antitumor immunopreventive and immunotherapeutic effects in mice by the fusion cancer vaccine of bone marrow derived dendritic cells and NS 1 myeloma cells

Aims: Further to study in vivo induction of host antitumor immunoprotective responses actively immunized with fusion cells based cancer vaccine of dendritic cells (DC)and cancer cells and its immunotherapeutical effects on tumor bearing mice.Methods:A large number of bone marrow derived DCS with high purity were generated with a combination of fresh isolation and in vitro cytokines induced expansion procedures established in our laboratory,and then fused with NS 1 myeloma cells using 50% polyethylene glycol (PEG) fusion protocol.The fusion cells were selected by culturing in the presence of HAT and HT cytokines,and then intravenously injected into mice to investigate antitumor immune preventative and therapeutic effects.Results:The fusion cells could stimulate proliferation of mixed T lymphocytes in vitro,but NS 1 cells could not.Normal mice vaccinated with lively fused cells for the first time were induced to develop more potent cytotoxic T lymphocytes (CTL) activity against parental NS 1 cells,and led to the resistance specially against the challenge and rechallenge of wild live parental tumor cells for more than 90 days.After treatment with alive fusion cells,the surval time of tumor bearing mice was greatly extended and the tumor volume increased very slowly or did not,or even decreased compared to cnotrol mice.Conclusions:These results suggest that active immunization with the fusion cells of dendritic and tumor cells as a cancer vaccine could induce effectively antitumor inmmune responses,and that it is likely to become a new way of tumor prevention and treatment.