树突状细胞与胃癌细胞融合的肿瘤疫苗研究

Effect of tumor vaccine prepared by fusion of gastric cancer cells with dendritic cells

目的以肿瘤细胞与树突状细胞(dendriticcells,DCs)相融合使融合细胞能将肿瘤抗原递呈给T细胞,并提供T细胞激活所必需的第二信号,借此激活机体的抗肿瘤免疫。方法通过PEG法将鼠源性胃癌细胞MFC与小鼠DC进行融合(T/DC),融合后经50Gy电子线照射,以1×106肿瘤疫苗于小鼠皮下注射免疫2次,间隔1周后接种,后一次免疫后1周于小鼠皮下接种5×105MFC胃癌细胞。肿瘤细胞接种3周后处死实验动物,测量肿瘤大小、外周血NK活性和脾细胞CTL活性。结果肿瘤接种后一周对照组小鼠皮下均有肿瘤生长,而T/DC免疫组均无皮下可触及的肿瘤(10/10),10天后T/DC免疫组才有4/10只鼠皮下出现可触及的肿瘤,3周后对照组肿瘤体积明显大于T/DC免疫组。经T/DC免疫后小鼠生存期明显较对照组延长,对照组于肿瘤接种后2周开始有小鼠衰竭死亡,至肿瘤接种后3周对照组仅有3只存活,T/DC免疫组有8只鼠存活,并仍有3只无肿瘤生长。经T/DC免疫后,小鼠NK活性和肿瘤特异性CTL活性均明显提高,T/DC免疫组和对照组MFC特异性CTL活性分别为30.09%和7.12%。结论肿瘤细胞鄄DC融合的肿瘤疫苗可通过加强抗原递呈激活肿瘤特异性CTL而具明显的抗肿瘤活性。

Objective To investigate the anti-tumor effect of tumor vaccine prepared by fusion of gastric cancer cells with dendritic cells. Methods Murine gastric cancer cells MFC were fused with dendritic cells derived from mice splenocytes by means of polyethylene glycol (PEG). The fused cells were irradiated at a dose of 50 Gy. Mice of the study group were immunized by injection 1×106 T/DC vaccine s.c. twice with an interval of one week. Mice of the control group received no vaccine at all. Both the T/DC immunized mice and those of the control gruop were inoculated 5×105 MFC gastric cancer cells subcutaneously. After three weeks at all tumor cell inoculation, all the mice were sacrificed. NK cell activity in peripheral blood lymphocytes(PBL) and cytotoxic T-lymphocytes (CTL) activity in splenocytes were tested. Results After one week of tumor inoculation, tumor grew in all the mice of the control group , while no tumor was found in any of the T/DC group. After ten days of tumor inoculation, tumors started to be palpable in 4 of the 10 mice of the T/DC group. By day 21, the mean volume of tumor in the control group was significantly larger than that of the T/DC group (1.829 cm2 vs 0.732 cm3 ). T/DC tumor vaccine could prolong the survival time of the study group; the 3-week survival rate of the control group was 30% (3/10), and that of the T/DC group was 80% (8/10). The NK cell activity in PBL of the T/DC group were higher than that of the control group ( 5.90% vs 9.30%). The tumor specific CTL activity of the T/DC group was also higher than that of the control group (30.09% vs 7.12%). Conclusions Irradiated tumor cells-DC cells fusion vaccine does possess the ability to stimulate anti-tumor immunity and improve the overall survival rate.