Antibody-drug conjugate mechanism (targeted drug delivery)
Core concept
- A monoclonal antibody used as a delivery vehicle for a cytotoxic too toxic to give systemically
- Three components, each of which determines behaviour
- 1. Antibody - defines the target antigen and therefore the tumour selectivity
- 2. Linker - cleavable (pH-, protease- or glutathione-sensitive -> payload released in the tumour microenvironment -> bystander killing of antigen-negative neighbouring cells) or non-cleavable (payload released only on lysosomal degradation -> no bystander effect, less off-target toxicity)
- 3. Payload - typically a microtubule inhibitor (MMAE, DM1) or topoisomerase I inhibitor (deruxtecan, SN-38)
- Drug-to-antibody ratio (DAR) determines potency and toxicity
- Sequence: antigen binding -> internalisation -> lysosomal trafficking -> payload release -> apoptosis
- *Efficacy does not require high antigen expression - trastuzumab deruxtecan works in "HER2-low" breast cancer*, because bystander killing does the rest
3 more sections, plus exam facts
Premium unlocks every note across every specialty, and the full exam fact library behind it.
Get premium access