Site-specific conjugation & linker chemistry
Site-specific conjugation and linker chemistry decide exactly where and how many payloads attach to the antibody, which determines how safe and effective an ADC is.
Overview
Random lysine or cysteine conjugation (T-DM1, brentuximab) gives heterogeneous mixtures. Engineered cysteines (THIOMAB), glycan remodelling (Synaffix GlycoConnect), enzymatic (sortase, transglutaminase), and non-natural amino acids (Ambrx, Sutro) yield homogeneous DAR. Hydrophilic linkers (Mersana Dolaflexin, Zymeworks ZD06519 platform, MediLink TMALIN) allow DAR 8 without aggregation; cleavable tetrapeptide GGFG (DXd) versus non-cleavable SMCC (T-DM1) governs bystander effect.
- Antibody
- Defined attachment sites (homogeneous DAR)
- Fab arm
How it works
Defined attachment sites and linker hydrophilicity control pharmacokinetics, aggregation, and payload release.
- Homogeneous product, better PK
- Enables high DAR and dual payloads
- Manufacturing complexity
Latest papers
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