宫颈癌与HPV16、18高危型别感染相关，HPV不同型别宫颈癌疫苗虽降低了疾病发病率，但对已经HPV感染、癌前病变、术后复发与转移等临床问题仍缺乏病毒特异的分子靶向治疗。基于亲和体的靶向药物有望实现新突破。本研究针对HPV早期表达肿瘤原性标志蛋白E7，在已筛选到HPV16、18E7亲和体基础上，构建HPV16/18E7双亲和体，负载颗粒酶B（GrB，免疫活性细胞产生的细胞毒效应分子），构建HPV16/18E7双亲和毒素发挥亲和体靶向识别（封闭E7致癌通路）和GrB细胞毒作用的双重优势。制备的双亲和毒素分别从蛋白、细胞、在体水平，及宫颈癌临床组织标本验证其靶向亲和特性；细胞株、荷瘤小鼠分析其靶向治疗效应及可能的分子机制；小鼠肝/肾功能、血液生理生化指标评估药物急毒作用。双亲和毒素可实现精准递送药物至靶细胞内，且同时靶向HPV16/18（覆盖面80%上），具备靶向药物研究的科学意义和临床价值。

Cervical cancer is associated with the infection of human papillomavirus (HPV) high-risk types of 16 and 18. Although HPV vaccines with different types against cervical cancer reduce the incidence of disease, there is still no targeted therapy for cervical cancer targeting virus-specific markers to deal with some clinical problems, such as, cervical precancerous lesions, recurrence and metastasis. An affinity molecule with high affinity to target protein has significant advantages, and perhaps can be put into practice. In this research, based on the groundwork of HPV16, or 18 monospecific affibody aimed at E7 (a oncogenic protein of HPV) by affinity screening, a bispecific affibody molecule double targeting to HPV16E7 and 18E7 (HPV16/18E7 affibody) will be conjugated, and fused with optimized human granzyme B (GrB, a kind of endogenous cytotoxic effector molecules produced by immunocompetent cells) to construct a HPV16/18E7 affinity toxin (affitoxin) in order to play the dual advantages of targeted affinity from affibody and cytotoxicity from GrB for dual fixed-point attack (blocking E7 to release cancer suppressive factor + cytotoxicity). The target affinity of HPV16/18E7 affitoxin will be confirmed on target proteins, or target cells, or in vivo, or in clinical tissue specimens, respectively. The targeting therapeutic effect of affitoxin on cell line and in tumor-bearing mice, and its possible molecular mechanism were investigated. The acute toxicity was assessed by liver/kidney function and blood physiological and biochemical indexes. This affitoxin can delivery the loaded drugs accurately into the target cells, and be dual targeting to HPV16/18E7 (coverage above 80% of cervical cancer), which has scientific significance and clinical value in the targeted drugs for cervical cancer.