我国是全球鼻咽癌的高发区，迄今尚无特异性方法防治鼻咽癌。EBV感染与鼻咽癌发生密切相关，其表达的LMP1和LMP2蛋白胞浆区结构域，可通过调控细胞内多条信号通路发挥致癌作用。因此，阻断LMP介导的信号调控是特异性治疗鼻咽癌的重要途径。基于单克隆抗体的肿瘤靶向治疗临床效果显著，但抗体渗透性差难以对胞内靶标发挥作用。亲和体(affibody)分子具有亲和力高、渗透性强和免疫原性弱等特性，在作用细胞内靶标时具有独特的优势。本项目拟通过噬菌体展示技术，分别筛选与LMP1和LMP2蛋白胞浆区结合的亲和体分子；并制备携带导向载体和穿膜肽的LMP1-LMP2双靶点亲和体分子，作为阻断LMP介导信号通路的效应分子；通过SPR、细胞免疫荧光、荷瘤裸鼠肿瘤成像和靶向治疗、及信号蛋白检测等技术方法，体内外实验验证该双靶点亲和体分子对鼻咽癌细胞的靶向结合及抗肿瘤作用机制。为特异性分子靶向治疗鼻咽癌提供全新途径。

China is a high incidence area of nasopharyngeal carcinoma in the world, so far there is no specific method to prevent and treat nasopharyngeal carcinoma. The latent infection of EB virus is closely related to the pathogenesis of malignant tumors such as human nasopharyngeal carcinoma, The cytoplasmic domains of LMP1 and LMP2 protein expressed by EBV can regulate multiple signaling pathways in cells and play a carcinogenic role. Therefore, blocking or inhibiting LMP-mediated signal regulation is one of the important approaches for specific treatment of nasopharyngeal carcinoma. Currently, Molecular targeted therapy based on monoclonal antibodies has achieved remarkable clinical results, however, it is difficult to penetrate the cell membrane and to play a role in intracellular targets because of its poor penetration. Affibody molecule has the characteristics of high affinity, strong permeability and weak immunogenicity, therefore, it has unique advantages in targeted therapy, especially in targeting intracellular targets. In this study, we intend to screen the EBV LMP1 and LMP2 protein cytoplasmic regions specific binding affibody molecule by using phage display technology, at the same time, to prepare LMP1 and LMP2 bispecific binding affibdoy molecules with the targeting carrier molecule and membrane-penetrating peptide as a therapeutic molecule to block intracellular LMP-mediated signaling pathway, and to validate molecular targeting binding and anti-tumor mechanism for nasopharyngeal carcinoma tumor cells in vivo and in vitro by SPR, immunofluorescence, imaging and treatment of nude mice bearing tumors, and detection of cell signaling pathway proteins etc. The study may provide a new approach for specific targeted therapy of EBV-related tumors such as nasopharyngeal carcinoma based on bispecific affibody molecule.