Bioanalysis in the development of antibody-drug conjugates
10.16438/j.0513-4870.2015-0792
- VernacularTitle:抗体偶联药物研发中的生物分析
- Author:
Xiu-li LI
1
;
Xiao-yan CHEN
1
;
Da-fang ZHONG
1
Author Information
1. Shanghai Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:REVIEWS
- Keywords:
antibody-drug conjugate;
drug-to-antibody ratio;
immunogenicity;
enzyme-linked immunosorbent assay;
LC-MS
- From:
Acta Pharmaceutica Sinica
2016;51(4):517-
- CountryChina
- Language:Chinese
-
Abstract:
Antibody-drug conjugates (ADCs) are complex molecules with cytotoxic small molecular drugs covalently bound to monoclonal antibodies via a linker and can improve the targeted drug delivery with minimizing the systemic toxicity. ADCs are heterogeneous mixtures with different drug-to-antibody ratios (DARs) and the DAR distribution is dynamically changing in vivo, therefore the bioanalysis of the ADCs is challenging. Enzyme-linked immunosorbent assay (ELISA) and LC-MS have been widely used in the ADCs bioanalytical assays. Just like other biotherapeutics, ADCs may elicit the host immune response and produce the anti-therapeutic antibody (ATA), which could affect its efficacy, pharmacokinetics, and safety. It is thereby important to investigate its immunogenicity in the ADC development. In this review, we summarized the ELISA- and LC-MS-based bioanalysis strategies for the development of ADCs, including DAR distribution, the determination of total antibody, conjugated antibody, conjugated drug, free drug, and ATA, with the expectation of providing insights and reference for the ADC development in China.
