학술논문

Antibody-drug conjugates: integrated bioanalytical and biodisposition assessments in lead optimization and selection
Document Type
Original Paper
Source
AAPS Open. 4(1)
Subject
Antibody-drug conjugates
Immunoassay
LC-MS
Biodisposition
CD74
CD25
GLP1R
GCGR
Language
English
ISSN
2364-9534
Abstract
Therapies based on monoclonal antibodies (mAbs) have delivered an impressive success in the clinics due to their exquisite specificity, potential for agonistic or antagonistic responses, tunable effector function, and optimal pharmacokinetic properties. Building on these inherent antibody properties, the design and development of antibody-drug conjugates (ADCs) with improved or gained therapeutic activity and safety has been successfully demonstrated in oncological applications. There is enormous potential for this new type of hybrid biologics but there are also significant engineering, manufacturing and bioanalytical challenges. In this manuscript, we highlight the range and diversity of assays that are critical to characterize the individual components of ADCs-linker, carrier, and payload. We discuss a series of in vitro and in vivo preclinical experimental approaches we implemented to characterize two anti-inflammatory steroid bearing ADCs, and an ADC bearing a modified glucagon-like peptide 1 receptor/glucagon receptor co-agonist peptide.