Date

Wednesday 02 Sep 2026

Time

15:30 - 16:00

Location

BW029

Supervisor

Sander van Kasteren

Jury

Marco van Eijk

Antibody-drug conjugates (ADCs) are "magic bullets" designed for targeted cancer therapies. They combine the extreme specificity of a monoclonal antibody (mAb) with a cytotoxic payload to achieve optimal tumour eradication. Although over 15 ADCs have already been approved by the FDA, their therapeutic index remains narrow in clinical practice. Many well-established targets, such as HER2, EGFR and c-Met, exhibit over-expression on tumour cells but are also expressed on healthy tissues, thereby leading to on-target, off-tumour toxicity. Consequently, certain highly selective tumour antigens, such as EpCAM, currently remain undruggable due to these toxicity limitations.

To address these limitations, this review focuses on next-generation bio-engineering strategies designed to optimize ADCs through antibody masking, Fc-region engineering and the manipulation of intracellular trafficking. While chemical linker stability is recognized as an absolute prerequisite, a hyper-stable, site-specific conjugation platform is used as a baseline in this review. This is because biological masking technologies can only function if the payload remains fully intact within the circulation.