The Power of Precision – Antibody Drug Conjugates in Modern Oncology

Antibody-drug conjugates (ADCs) provide a powerful approach for cancer treatment. Their precise targeting and potent cell-killing effects make them a hot topic in the development of anticancer drugs. Since the US Food and Drug Administration (FDA) approved the first ADC drug Mylotarg® (gemtuzumab ozogamicin) in 2000, 14 ADCs have been approved for marketing worldwide. Currently, more than 100 ADC candidates are in clinical trials. The chemistry behind ADC design plays a crucial role in their targeting and delivery. Key factors include the selection of antibodies, cytotoxic payloads, chemical linkers, and conjugation methods, which influence the drug-to-antibody ratio (DAR), therapeutic efficacy, stability, and safety. Techniques such as click chemistry, cysteine or lysine-specific conjugation, and site-specific conjugation methods, including enzymatic or chemical cleavable linkers, are essential to ensure uniform DAR and minimal off-target effects. Advances in bioconjugation techniques like hydrophobic interaction chromatography (HIC) and size-exclusion chromatography (SEC) are also used to assess and refine ADCs. Many of these drugs show great promise for the treatment of cancers, although challenges remain, including systemic toxicity, insufficient biomarkers for patient selection, acquired drug resistance, and unknown benefits of combination with other cancer therapies. This seminar will explore the development of ADCs in oncology, focusing on their design, characterization, and application.