论文部分内容阅读
PD-1是参与免疫抑制调节、肿瘤免疫逃逸的重要因子之一。通过抑制PD-1,可以提高T细胞的活性、细胞因子的分泌水平,从而提高抗肿瘤效果。本研究通过基因重组,构建了小鼠PD-1胞外结构域蛋白m PD-1和m PD-1与喉毒素跨膜结构域(DTT)融合的DTT-m PD-1蛋白。蛋白经大肠杆菌表达后,由镍柱亲和纯化。用蛋白疫苗免疫Balb/c小鼠后发现,DTT-m PD-1蛋白没有在小鼠体内产生抗PD-1的免疫反应。但是,先用DTT免疫三次(隔两周免疫一次),再用m PD-1免疫小鼠,反而引起了抗PD-1的免疫反应,血清效价高达7×104。这一发现,为肿瘤免疫治疗提供了一种全新的方式。
PD-1 is involved in immunosuppression regulation, tumor immune escape one of the important factors. By inhibiting PD-1, T cell activity can be increased, the level of cytokine secretion, thereby enhancing the anti-tumor effect. In this study, DTT-m PD-1 protein was constructed by gene recombination to fuse mouse PD-1 extracellular domain proteins m PD-1 and m PD-1 with laryngeal toxin transmembrane domain (DTT). After the protein was expressed in E. coli, it was affinity purified by nickel column. Immunization of Balb / c mice with protein vaccines revealed that DTT-m PD-1 protein did not produce an anti-PD-1 immune response in mice. However, immunization with DTT three times (once every two weeks) and subsequent immunization with m PD-1 resulted in an anti-PD-1 immune response with serum titer of up to 7 × 104. This discovery provides a completely new way for cancer immunotherapy.