Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the therapeutic activity of small molecule payloads, enabling targeted delivery while minimizing off-target effects. Their potential in areas such as targeted cancer cell killing and targeted protein degradation has fueled significant growth, resulting in numerous FDA approvals and more than 100 ADCs currently in clinical development. However, ADC development remains complex and highly empirical, requiring careful optimization of linker chemistry, payload selection, bioconjugation strategies, drug-to-antibody ratio (DAR), stability, and overall antibody integrity.
The ADC journey begins with linker-payload synthesis and bioconjugation. Eurofins Discovery offers extensive expertise in the design and synthesis of linker technologies, including protease-sensitive, glycosidase-sensitive, pH-sensitive, PEGylated, branched, and shielding linkers. Payloads are manufactured in specialized high-containment facilities to ensure the safe handling of highly potent compounds. Multiple conjugation options are available, providing flexibility to explore different designs and generate ADCs with customized pharmacokinetic profiles, improved stability, and controlled DAR distributions.
Once conjugation is complete, ADCs undergo purification using a range of chromatography techniques. These methods remove unconjugated antibodies, excess linker-payload materials, and aggregates to produce highly pure ADC preparations. This is essential for more reliable downstream analyses and ensures more accurate assessment of ADC performance.
DAR analysis is then conducted using high-resolution liquid chromatography-mass spectrometry (LC-MS). This approach confirms linker-payload incorporation, identifies individual DAR species, and provides detailed insights into ADC homogeneity. Such information is critical for optimizing product consistency, efficacy, safety, and manufacturability.
Finally, a comprehensive suite of biochemical, functional, and cytotoxicity assays is essential to characterize ADC candidates. Data-driven assessment of binding, biological function, and therapeutic potential, through both in vitro and in vivo studies, helps identify the most promising candidates for further advancement and development.
Eurofins Discovery provides a fully integrated ADC development platform spanning every stage of the workflow, from linker-payload design through analytical characterization and functional assessment. By leveraging deep expertise in chemistry, biochemistry, and antibody optimization and characterization, Eurofins Discovery scientists help mitigate development risks and shorten timelines while optimizing ADC safety, efficacy, and manufacturability.