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基于高低亲和力抗犬PD-L1抗体与肿瘤微环境响应性连接子的抗体偶联药物制备及初步性能评估

PAN Zhiyuan WANG Chenguang QIAN Weizhu HOU Sheng JI Lusha LI Jun SUN Ziqiao WANG Xuekun XIE Lei ZHANG Dapeng GUO Huaizu REN Yule GUO Qingcheng XU Jin ZHU Weifan ZHUANG Huangzhen GAO Tianyu CHEN Yi GUO Menghui LIU Tao

聊城大学学报（自然科学版）2026，Vol.39Issue(1)：94-105,12.
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聊城大学学报（自然科学版）2026，Vol.39Issue(1)：94-105,12.DOI:10.19728/j.issn1672-6634.2025030005

基于高低亲和力抗犬PD-L1抗体与肿瘤微环境响应性连接子的抗体偶联药物制备及初步性能评估

Preparation and preliminary evaluation of antibody-drug conjugates targeting canine PD-L1 using high/low affinity anti-PD-L1 antibodies and tumor microenvironment-responsive linkers

PAN Zhiyuan 1WANG Chenguang 2QIAN Weizhu 3HOU Sheng 3JI Lusha 3LI Jun 3SUN Ziqiao 3WANG Xuekun 4XIE Lei 3ZHANG Dapeng 3GUO Huaizu 4REN Yule 1GUO Qingcheng 2XU Jin 3ZHU Weifan 1ZHUANG Huangzhen 1GAO Tianyu 1CHEN Yi 1GUO Menghui 1LIU Tao5

作者信息

  • 1. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences and Food Engineering,Liaocheng University,Liaocheng 252059,China||NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China
  • 2. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences and Food Engineering,Liaocheng University,Liaocheng 252059,China||NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China||State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China||Taizhou Mabtech Pharmaceuticals Co.,Ltd.,Taizhou 225316,China
  • 3. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences and Food Engineering,Liaocheng University,Liaocheng 252059,China||NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China||State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China
  • 4. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences and Food Engineering,Liaocheng University,Liaocheng 252059,China||NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China||State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China||State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,Shanghai Zhangjiang Biotechnology Co.,Ltd.,Shanghai 201203,China
  • 5. State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences and Food Engineering,Liaocheng University,Liaocheng 252059,China||NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China||State Key Laboratory of Macromolecular Drugs and Large-scale Preparation,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China||Department of Oncology,Huashan Hospital,Fudan University,Shanghai 200040,China
  • 折叠

摘要

Abstract

Immune checkpoint blockade therapies have made groundbreaking progress in human cancer treatment,but the development of immunotherapeutic drugs for canine tumors remains a significant chal-lenge.With the rise of the pet market and advancements in veterinary medical technology,the demand for antibody-drug conjugates(ADCs)targeting canine tumors is growing.However,research on ADCs targe-ting canine Programmed Death-Ligand 1(PD-L1)is still in its infancy,with issues such as drug resistance and insufficient therapeutic efficacy requiring further exploration,particularly the impact of different anti-body types and drug-to-antibody ratio(DAR)on novel ADC performance.This study pioneers the prepa-ration of two novel canine PD-L1-targeting ADCs by integrating high/low-affinity anti-canine PD-L1 mon-oclonal antibodies(A-mAb and T-mAb),tumor microenvironment-responsive linkers,and the next-gen-eration topoisomerase I inhibitor Dxd.Through controlled conjugation parameters,ADCs with distinct DAR values were successfully prepared.Subsequent characterization,stability analysis,binding activity,and cytotoxicity evaluation revealed that both ADCs exhibited well-controlled DAR values and favorable developability.DAR values and antibody types influenced ADC stability and activity,while both high-and low-affinity antibodies demonstrated dose-dependent cytotoxicity that intensified with increasing DAR val-ues.This study lays the foundation for developing PD-L1-targeting ADCs for canine tumors and provides candidate drugs for future caninized ADC development.

关键词

抗体药物偶联物/犬类肿瘤/免疫疗法/程序性死亡受体配体1/药物抗体偶联比

Key words

antibody-drug conjugates(ADCs)/canine tumors/immunotherapy/programmed death-ligand 1(PD-L1)/drug-to-antibody ratio(DAR)

分类

农业科技

引用本文复制引用

PAN Zhiyuan,WANG Chenguang,QIAN Weizhu,HOU Sheng,JI Lusha,LI Jun,SUN Ziqiao,WANG Xuekun,XIE Lei,ZHANG Dapeng,GUO Huaizu,REN Yule,GUO Qingcheng,XU Jin,ZHU Weifan,ZHUANG Huangzhen,GAO Tianyu,CHEN Yi,GUO Menghui,LIU Tao..基于高低亲和力抗犬PD-L1抗体与肿瘤微环境响应性连接子的抗体偶联药物制备及初步性能评估[J].聊城大学学报（自然科学版）,2026,39(1):94-105,12.

基金项目

国家自然科学基金项目(22304067) （22304067）

上海东方英才项目(CYQN2023031) （CYQN2023031）

山东省自然科学基金(ZR2023QB257,ZR2023QB196) （ZR2023QB257,ZR2023QB196）

山东省高等学校"青创团队计划"团队(2022KJ111) （2022KJ111）

光岳青年学者创新团队项目(LCUGYTD2022-04)资助 （LCUGYTD2022-04）

聊城大学学报（自然科学版）

1672-6634

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