Enzymes for ADC Production
Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAb) covalently linked to a cytotoxic drug via a chemical linker. ADC was conceived to bridge the gap between the mAb and cytotoxic drug for the improvement of specific targeting ability and killing effect. No fewer than fifteen ADCs have been approved or are under regulatory review in different countries worldwide.
The key quality attributes (drug antibody ratio) of ADCs are affected by conjugation methods, including random coupling and site-specific conjugation. Site-specific conjugation can help reduce the heterogeneity of ADCs.
Enzyme-mediated glycan conjugation, glycan remodeling and glycoengineering at the N297 position of IgG Fc fragment can generate site-specific ADCs. The widely used enzymes in ADC production include Peptide-N-glycosidase (PNGase F), bacterial transglutaminase (BTG), Sortase A (SrtA), β1,4-galactosidase, β1,4-galactosyltransferase (Gal T), α2,6-sialyltransferase (Sial T), Endo-N-acetylglucosaminidase (ENGase), Endoglycosidase S (EndoS), and Glycosyltransferases (GTs).
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Application
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Enzymes
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Function
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Enzyme-mediated glycan conjugation
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Peptide-N-glycosidase (PNGase F)
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Cleaves the amide bond between the first saccharide GlcNAc and the Asn297 side chain L; Release glycans from IgG antibodies.
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Bacterial transglutaminase (BTG)
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Conjugate payloads site-specifically to generate ADCs.
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Sortase A (SrtA)
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Catalyze the ligation of proteins.
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β1,4-galactosidase
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Release all terminal galactoses and form a homogenous G0 isoform of the antibody.
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β1,4-galactosyltransferase (Gal-T)
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Transfer a sugar residue with a chemically reactive functional group.
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α2,6-sialyltransferase (Sial T)
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Incorporate terminal sialic acid residues into the native glycan structure of an antibody.
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Enzyme-mediated glycan remodeling and glycoengineering
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Endo-N-acetylglucosaminidase (ENGase)
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Hydrolyze the β1,4-glycosidic bond between GlcNAcβ1–4GlcNAc of N-glycans; Remove N -linked glycans on the Fc region of IgG antibodies.
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Endoglycosidase S (EndoS)
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Glycosyltransferases (GTs)
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Transfer N-glycan oxazoline to defucosylated IgGs.
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