PD-1/PD-L1免疫检查点信号通路的阻断能够有效改善机体对多种肿瘤的免疫应答，引发持久抗肿瘤反应。现有阻断PD-1/PD-L1信号通路的抗体药物存在治疗效率低和引发自身免疫疾病的问题。开发高效阻断PD-1/PD-L1信号通路的新靶标和阻断试剂是提高免疫检查点肿瘤免疫疗法效率以及安全性的重要策略。不同于经典抗体通过靶向蛋白质的多肽结构域来阻断信号通路，本研究利用分子印迹技术，设计和制备识别肿瘤细胞PD-L1的N-糖的人工抗体，研究以信号通路糖蛋白PD-L1的N-糖为靶标调控PD-L1介导的肿瘤免疫抑制效应，用于肿瘤免疫治疗。本项目的开展将建立靶向蛋白质翻译后修饰N-糖的人工抗体的制备方法，填补靶向N-糖试剂的短缺；阐明以PD-L1的N-糖为靶标调控肿瘤免疫抑制效应的机制；探究靶向PD-L1的N-糖的人工抗体用于肿瘤免疫治疗的可行性，为肿瘤免疫治疗药物的开发提供新思路。

Blocking PD-1/PD-L1 immune checkpoint signaling pathway can effectively improve the body’s immune response to a variety of tumors and trigger a durable anti-tumor response. Existing antibody drugs that block the PD-1/PD-L1 signaling pathway suffer from low treatment efficacy and risk of causing autoimmune diseases. The development of new targets and blocking agents that efficiently block the PD-1/PD-L1 signaling pathway is an important strategy to improve the efficacy and safety of immune checkpoints based tumor immunotherapy. Different from classical therapeutic antibodies, which block the signal pathway by targeting the polypeptide domain of the protein, the present research takes advantages of molecular imprinting technology to design and prepare artificial antibodies that can specifically recognize the N-glycans of PD-L1 on tumor cells. Furthermore, the mechanism of regulating the PD-L1-mediated immunosuppressive effects of tumors as well as the tumor immunotherapy by targeting the N-glycans of PD-L1 will be investigated. Based on the present research, the method for preparing artificial antibodies that target post-translationally modified N-glycans of proteins will be established, which can fill the shortage of targeting reagents specific to post-translationally modified N-glycans. Besides, the mechanism of regulating the PD-L1-mediated immunosuppressive effects of tumors by targeting the N-glycans will be clarified and the feasibility of the prepared N-glycans-targeting artificial antibodies for tumor immunotherapy will be verified, which can provide new possibilities for the development of cancer immunotherapy drugs.