OnCo
termsTerm

Linker (ADC)

The linker is the chemical tether between antibody and payload. It must hold in the blood and let go inside the tumour.

Cleavable linkers (protease-sensitive peptides like Val-Cit or GGFG, acid-labile hydrazones, glutathione-sensitive disulfides) release free payload; non-cleavable linkers (SMCC in T-DM1) release payload still attached to an amino acid, which cannot cross membranes. Linker hydrophilicity permits high DAR without aggregation.

ADC: what this kind of term is about · animated schematic, not to scale
Category
ADC

Key papers

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rctNew England Journal of Medicine 2021changed practice
ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer

Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.

Connected

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technologies

2
Antibody-drug conjugate (ADC)Site-specific conjugation & linker chemistry

drugs

1
ApprovedADC
Inotuzumab ozogamicin · Besponsa

terms

10
Acid-labile hydrazone (AcBut)CL2AHydrophilic next-generation linkers (TMALIN, Dolaflexin, sulfonyl-pyrimidine, PEG-containing)Maleimidocaproyl (mc), non-cleavablemc-Val-Cit-PABCProdrugSMCC (thioether, non-cleavable)Sulfo-SPDB (disulfide)Tetrapeptide GGFG (maleimide-GGFG-aminomethyl)Val-Ala dipeptide

ideas

1
Platform designation for ADC linker-payloads so manufacturing data carry across

key papers

1
ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer