Multiepitope recognition technology promotes the in-depth analysis of antibody‒drug conjugates.
10.1016/j.apsb.2024.06.007
- Author:
Yutian LEI
1
;
Yuan SHEN
2
;
Feng CHEN
1
;
Rui HE
1
;
Zhang ZHANG
1
;
Ying ZHOU
1
;
Jin-Chen YU
3
;
Jacques CROMMEN
1
;
Zhengjin JIANG
1
;
Qiqin WANG
1
Author Information
1. Institute of Pharmaceutical Analysis, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China.
2. Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China.
3. Bio-Thera Solutions, Ltd, Guangzhou 510700, China.
- Publication Type:Journal Article
- Keywords:
Affinity enrichment;
Antibody‒drug conjugate;
Biotransformation;
LC‒MS;
Multiepitope recognition strategy
- From:
Acta Pharmaceutica Sinica B
2024;14(11):4962-4976
- CountryChina
- Language:English
-
Abstract:
The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs. MERT's excellent specificity, ultrahigh ligand density, and potential synergistic recognition ability enable it to target the different key regions of ADCs to overcome the deficiencies of traditional technologies. The binding capacity of MERT for antibodies is ten to hundred times higher than that of the mono-epitope or Fc-specific affinity technologies. Since MERT can efficiently capture target ADCs from serum, a novel bioanalytical platform based on MERT and RPLC‒QTOF-MS has been developed to monitor the dynamic changes of ADCs in serum, including the fast changes of drug-to-antibody ratio from 3.67 to 0.22, the loss of payloads (maytansinol), and the unexpected hydrolysis of the succinimide ring of the linker, which will contribute to clarify the fate of ADCs and provide a theoretical basis for future design. In summary, the MERT-based versatile platform will open a new avenue for in-depth studies of ADCs in biological fluids.
