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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.
Defined attachment sites and linker hydrophilicity control pharmacokinetics, aggregation, and payload release.
Nothing recorded yet: a foundation, or a gap to fill.
Dependencies are what this technology cannot be delivered without: manufacturing steps, instruments, software, upstream methods. See its full chain on the map.
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.
Query 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.
Shares ACE-Breast-02, ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03), ARX788, HER2-positive breast cancer.
Shares Drug-to-antibody ratio (DAR), Linker (ADC), Antibody-drug conjugate (ADC).
Shares Synaffix (Lonza), ADC bioconjugation manufacturing (CDMOs), The ADC supply chain (antibody, payload-linker, conjugation, fill).
Shares Dual-payload ADCs in first line to prevent resistance, Dual-payload ADC.
Shares Sutro Biopharma, Luveltamab tazevibulin.
Shares ADC bioconjugation manufacturing (CDMOs), The ADC supply chain (antibody, payload-linker, conjugation, fill), Antibody-drug conjugate (ADC).
Shares ADC bioconjugation manufacturing (CDMOs), The ADC supply chain (antibody, payload-linker, conjugation, fill).
Shares Antibody-oligonucleotide conjugates, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, Antibody-drug conjugate (ADC).