恶性肿瘤的的发生、发展、转移均需要充足的血液供应，肿瘤部位血管生成对于肿瘤的生长和转移提供氧气及营养至关重要。VEGF是肿瘤血管生成中起最主要作用的激活因子，肿瘤血管新生主要通过VEGF/KDR通路来直接增强肿瘤的生长。NRP1作为VEGF的非酪氨酸激酶受体，其存在大大增强了VEGF与KDR的结合能力，是肿瘤血管新生，肿瘤侵袭、转移的重要增强子，并在介导Treg细胞发挥抗肿瘤免疫、免疫自稳发面发挥着重要作用。研究发现采用抗VEGF类药物进行治疗时，机体会代偿性地高表达NRP1等因子，使得抗VEGF类的抗血管生成药物治疗失败。本研究结合临床实际，拟制备抗人NRP1单克隆抗体，结合前期工作中获得的抗人KDR单链抗体、重组蜂毒肽，制备出携带蜂毒肽的具有靶向抑制NRP1、KDR的双靶点新型抗体，以双重闭锁的方式阻断肿瘤血管生成，并发挥蜂毒肽的强大溶细胞活性，为肿瘤血管靶向治疗提供新思路、新材料。

The occurrence, development and metastasis of malignant tumors requires adequate blood supply, and tumor angiogenesis is vital to tumor growth and metastasis for providing O2 and nutrition. VEGF is the most important angiogenesis promoting factor, tumor angiogenesis is mediated primarily through the VEGF / KDR pathway to directly enhance tumor growth. NRP1 as a non tyrosine kinase receptor of VEGF, its presence greatly enhanced the binding ability between VEGF and KDR. In tumor angiogenesis, NRP1 is an important enhancer in tumor invasion and metastasis. NRP1 is also required by Treg cells to limit anti-tumour immune responses and immune homeostasis. Lots of studies found that the use of anti-VEGF drugs for tumor treatments met drug resistance which led the failure of therapy because of the compensatory expression of other growth factors, such as NRP1, in patients or animals treated. In this study, firstly, we plan to preparate monoclonal antibodies against human NRP1. Secondly, based on the single chain antibody of KDR and reconstructed melittin which we have already generated respectively, a novel dual-to-one antibody which has the ability of inhibiting NRP1, KDR and the activity of mellitin will be generated and characterized. The novel antibody would have strong ability to block tumor angiogenesis in a dual-locking manner to block tumor angiogenesis and have the strong cytolytic activity in local tumor. The generation of the novel antibody will provide new material and good idea for anti-angiogenic tumor therapy in the future.