GM-CSF基因瘤苗抗肿瘤活性的实验研究

EXPERIMENTAL INVESTIGATION ON THE TUMOR VACCINE ENGINEERED WITH hGM-CSF GENE

转细胞因子基因的肿瘤细胞疫苗是当今肿瘤免疫－基因治疗研究的热点。本文用逆转录病毒载体将人粒细胞－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）基因转入大鼠Ｗａｌｋｅｒ瘤细胞株ＷＲＣ２５６，经Ｘ－射线灭活制备肿瘤疫苗。经ＰＣＲ和Ｓｏｕｔｈｅｒｎｂｌｏｔ检测证实。ＧＭ－ＣＳＦ基因已成功地导入ＷＲＣ２５６细胞。生物学活性检测表明，灭活前后的转基因瘤细胞均能持续分泌ＧＭ－ＣＳＦ。动物试验结果表明，转基因瘤苗具有明显的抗肿瘤活性。并能诱导具有杀死瘤细胞功能的特异性细胞毒Ｔ淋巴细胞（ＣＴＬ）。本工作对细胞因子基因瘤苗的研究及临床应用将具有重要意义。

The gene-transferred tumor vaccine is a new interesting advance in the field of antitumor research. Oberservation was made on the antitumor effects of such vaccine on rat Walker tumor. In our study, it is demonstrated that although the growth of the tumor in untransferred vaccine group (GM-CSF) was similar to that in control group(c), there had a significant difference in the tumor size and weight between gene-transferred vaccine group (GM+) and the control group(c). The pathological examination revealed the massive leukocyte infiltration in the tumor tissue of the gene-transferred vaccine group, but rarely in the control group and untransferred group. Spleen CTL cytotoxicity assay showed that the cytotoxicity of spleen CTL in the gene-transferred vaccine group to WRC256 cells were much more powerful than that in control group. These results suggested that the gene-transferred tumor vaccine have induced an immunoresponse in which specific CTL plays an important role against the tumor in vivo.