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.
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.
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
ARX788 is a HER2 ADC with a precisely placed, non-cleavable payload that beat lapatinib-capecitabine in China and showed activity in brain metastases.
A folate-receptor ADC designed to work across low and high receptor levels, in a pivotal ovarian cancer trial.
Latest papers
topQuery for this technology: (TITLE:"site-specific conjugation" OR ABSTRACT:"site-specific conjugation" OR TITLE:"drug-to-antibody ratio" OR ABSTRACT:"drug-to-antibody ratio" OR TITLE:"ADC linker" OR ABSTRACT:"ADC linker"). Results are unfiltered search hits about Site-specific conjugation & linker chemistry, not a curated reading list.
Pages like this
not linked directly; found by shared links- TermHydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)
Shares Drug-to-antibody ratio (DAR), Linker (ADC), Antibody-drug conjugate (ADC).
- TechnologyDegrader-antibody conjugate (DAC)
Shares Antibody-oligonucleotide conjugates, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, Antibody-drug conjugate (ADC).
- CompanyLonza
Shares Synaffix (Lonza), ADC bioconjugation manufacturing (CDMOs).
- IdeaSequencing HER2 ADCs by payload after T-DXd
Shares ARX788, HER2-positive breast cancer, Antibody-drug conjugate (ADC).
- ProductLapatinib
Shares ACE-Breast-02, HER2-positive breast cancer.
- TargetFolate receptor alpha
Shares Luveltamab tazevibulin, Sutro Biopharma, Antibody-drug conjugate (ADC).
- IdeaPayload-class switching as the rule for ADC sequencing
Shares Dual-payload ADCs in first line to prevent resistance, Dual-payload ADC, Antibody-drug conjugate (ADC).
- IdeaDose and schedule optimisation trials specific to antibody-drug conjugates
Shares Drug-to-antibody ratio (DAR), Antibody-drug conjugate (ADC).