ADC Development Workflows: From Linker Design to Characterization
Antibody-drug conjugates (ADCs) combine the antigen specificity of monoclonal antibodies with the therapeutic power of small molecule payloads, enabling functions including targeted tumor cell killing, targeted protein degradation, and others with fewer side effects. This precision has driven rapid expansion in the field, with more than 100 ADCs in active clinical trials and numerous FDA approvals in the past five years.
Despite this momentum, ADC work remains highly empirical, requiring strategic payload design, careful optimization of linker chemistry, payload potency, linker-payload stability, bioconjugation strategy, drug-to-antibody ratio (DAR), and antibody integrity, along with rigorous characterization in complex biological systems.
ADC Synthesis, Optimization, and Characterization, All Under One Roof
At Eurofins Discovery, we deliver comprehensive chemistry and biochemistry capabilities to support streamlined ADC optimization and characterization, including linker-payload synthesis, bioconjugation, and ADC biochemical and functional characterization. This unified workflow leverages our team of small molecule chemists and antibody experts to reduce iterative cycles of costly rework and de-risk development to avoid future safety concerns. Whether supporting a discrete stage or executing an end-to-end program, Eurofins Discovery can help you accelerate timelines and build ADCs optimized for safety, efficacy, and manufacturability.
Linker-Payload Synthesis and Bioconjugation
Eurofins Discovery can design and synthesize diverse payloads and linker systems, including pH-sensitive and protease-cleavable linkers, in an OEB5-certified facility designed for safe handling of cytotoxic materials. Our team and chemistry capabilities can support both stochastic and site-specific bioconjugation strategies, including glycan-based approaches. This flexibility allows you to compare conjugation methods, tune PK and stability properties, and generate ADCs with controlled DAR profiles.
- Linker synthesis
- Protease-sensitive
- Glycosidase-sensitive
- pH-sensitive
- PEGylated
- Branched
- Shielding
- Payload synthesis with high-containment capabilities
- Stochastic, site-specific, and glycan antibody bioconjugation
ADC Purification
Using size exclusion chromatography (SEC), our ADC experts can remove unconjugated antibodies, excess linker-payload, and aggregates, delivering highly pure ADC preparations. We employ multiple chromatography platforms to achieve clean separation of monomeric ADC species for more confident DAR analysis and downstream binding and functional testing.
- Analytical SEC
- Preparative SEC
Drug-to-Antibody ratio (DAR) Analysis
Following bioconjugation and purification, our team uses high-resolution LC-MS workflows to perform DAR analysis, confirming the linker-payload mass and identifying the different DAR species. This analysis provides precise, actionable insight into ADC heterogeneity, supporting further characterization and optimization of safety, efficacy, and manufacturability.
Binding and Functional Characterization
Eurofins Discovery has a robust and broad portfolio of biochemical, functional, and cytotoxicity assays to accelerate the identification of the most promising ADC candidates. Using both in vitro and in vivo assays, we enable data-driven ADC assessment and improve translational potential.
- Binding assays
- Internalization and endocytosis assays
- Proliferation assays
- Apoptosis assays
- Payload release assays
- Cytotoxicity assays
- Safety assessments
