Overview

ADCs are a class of drugs that use monoclonal antibodies to achieve targeted delivery of cytotoxic drugs to antigen-expressing cells. CD BioGlyco provides customers with ADC development services through site-specific conjugation based on glycan oxidation.

ADCs combine the targeting specificity of monoclonal antibodies with the potency of cytotoxic drugs to achieve targeted delivery of cytotoxic drugs to antigen-expressing cells, thereby enhancing therapeutic activity. ADCs generally consist of an antibody, a cytotoxic drug, and a linker between the two. During the development of ADC drugs, it is necessary to select monoclonal antibodies that recognize cell surface antigens and be endocytosed by cells. And cytotoxic molecules and coupling methods also need to be comprehensively considered. The traditional coupling method is to use drug linker reagents to non-specifically modify antibody lysine or cysteine residues, but this method has the problem of lack of specificity of coupling sites and the number of coupled small molecules. Therefore, the traditional coupling method is difficult to control the uniformity of the drug, and moreover,  the efficacy, biosafety, and kinetic parametersof ADCs with different payloads are also different. The site-specific conjugation of ADC can effectively solve this problem.

Site-Specific Conjugation

There are various methods to achieve site-specific conjugation, such as cysteine conjugation, glycoconjugation, incorporation of unnatural amino acids, peptide tags, etc. Cysteine residues are a classic method of site-specific protein modification by engineering or reducing native disulfide bonds to generate cysteine residues, which are then selectively reacted with many electrophiles. Glyco-based site-specific conjugation is based on human IgG molecules having a conserved glycosylation site at each N297 residue in the CH2 domain, making the N-glycans of the side chain site-specific conjugated target. Unnatural amino acids are incorporated into the antibody sequence via amber stop codon-mediated transcription, enabling site-specific conjugation. Biotin ligases and transglutaminases, etc. provide site-specific attachment of small molecules to peptide substrates in various proteins.

One Oxidation, Infinite Targets: Glycan-Adaptable ADC Platform.

Oxidative cleavage of the terminal cis-diol oligosaccharide results in an aldehyde group that is chemically reacted with some reagents containing aminooxy, hydrazine, or hydrazide functional groups. The reaction allows site-specific conjugation of the load to the antibody. Antibody glycans typically contain vicinal diols that are cleaved by oxidation to generate aldehyde groups. At CD BioGlyco, we oxidize the sugar group in the antibody's native glycan to an aldehyde group by the periodate oxidation method, and then the aldehyde group is combined with a small molecule hydrazide or aminooxy compound.

Case: The fucose in the antibody's native glycan is oxidized by sodium periodate (NaIO₄) and coupled to hydrazone. Thereby the drug-linker molecule binds to the N-glycan of IgG.

Workflow

• Initial Project Consultation

We begin with a detailed discussion to understand your specific needs, including antibody and payload characteristics, therapeutic targets, and project timelines. Our experts provide a comprehensive feasibility assessment and a customized plan.

• Glycan Remodeling and Activation

Your antibody is treated to create a uniform population of reactive glycan sites. This involves both enzymatic remodeling and the controlled periodate oxidation to generate the aldehyde groups required for conjugation.

• Optimized ADC Conjugation

The activated antibody is then conjugated with your drug-linker of choice. Our team optimizes reaction conditions to maximize conjugation efficiency and ensure the formation of a homogeneous product with a consistent DAR.

• Purification and Comprehensive Characterization

The resulting ADC is meticulously purified to isolate the homogeneous product and remove unreacted components. We then perform a full suite of characterization assays, including mass spectrometry and HPLC, to confirm the precise DAR, ensure product purity, and verify the integrity of the antibody.

• Preclinical Evaluation

We can support your preclinical development with a range of in vitro and in vivo studies, including assays for target-binding affinity, cytotoxicity, and in vivo efficacy in relevant disease models.

Publication Data

Advantages

• By precisely targeting the native N-glycosylation sites, our process consistently yields a highly homogeneous ADC.
• The reduced heterogeneity minimizes the risk of off-target toxicity, allowing for a wider therapeutic window.
• Our mild, non-invasive chemistry ensures that the structural integrity of the antibody is fully preserved.

Application

• This service can be used in attaching diverse payloads (e.g., toxins, fluorescent dyes, radioisotopes) to oxidized glycans, facilitating the creation of theranostic ADCs for real-time tracking and targeted therapy.
• This service can be used in generating ADCs with defined drug-to-antibody ratios by oxidizing Fc glycans to create aldehyde groups for site-specific payload conjugation, minimizing heterogeneity and improving pharmacokinetics.
• This service can be used in evaluating tumor-targeting efficacy and safety profiles of glycan-oxidized ADCs in xenograft models, accelerating translational research for cancers with high antigen expression.

Frequently Asked Questions

Associated Services

Glycan oxidation-based ADC development leverages controlled periodate cleavage of antibody glycans to enable site-specific conjugation—optimizing therapeutic homogeneity while preserving antigen-binding integrity. To extend this precision to quality validation across diverse pharmaceuticals, we offer Pharmaceutical Analysis Services that ensure purity, stability, and compliance through:

CD BioGlyco is committed to providing ADC development services utilizing glycosylation site-specific conjugation technology to meet the research needs of our clients. If you have glycan oxidation-based ADC development services, please feel free to contact us for more information.