Custom Glycosylation of Antibodies
Glycosylation Background in Antibody
Glycans, especially those attached to the IgG antibodies' glycosylation site at Asn297 on the Fc region, regulate interactions with Fc receptors and complement proteins, control clearance rates via hepatic pathways, and stabilize protein conformation. For recombinant antibody therapeutics, subtle shifts in glycan composition can translate into significant differences in clinical efficacy or immunogenicity. Studies on glycosylation and its impact on the pharmacokinetics of monoclonal antibodies have shown that sialylated Fc glycans extend serum half-life, while defucosylation boosts ADCC by improving FcγRIIIa engagement. Whether targeting antibodies against glycosylated proteins in colorectal cancer or refining anti-inflammatory IVIG analogs, optimizing glycosylation is no longer optional—it's essential. At Creative Biolabs, our custom glycosylation solutions help clients achieve precise glycoform control for robust antibody performance.
Fig.1 Diverse IgG Fc glycoforms and their functional impact.
Integrated Service for Tailored Antibody Glycosylation
Glycoengineering & Optimization
We offer custom glycosylation antibody development solutions tailored to your therapeutic goals—whether for enhanced efficacy, extended half-life, or reduced immunogenicity. Our team understands the complexity behind systems analysis of glycosylated antibodies: regulation, engineering and functions, and turns it into actionable, scalable solutions.
- Apply glycosylation site engineering of antibodies using gene-editing tools to manipulate specific sites (core fucosylation, galactosylation, and sialylation) and ensure functional glycoform expression.
- Fine-tune expression with metabolic control of recombinant monoclonal antibody N-glycosylation, adjusting pH, nutrient feed, and oxygenation to shape glycan output.
- Choose from CHO, HEK293, yeast, bacteria, or plant cells expression systems for glycosylated antibodies to match production scale and glycan fidelity.
- Engineer fucose-deficient variants or boost sialylation via targeted overexpression of glycosyltransferases, enhancing clinical performance.
Glycosylation Profiling & Analysis
Accurate glycan characterization underpins every successful glycoengineering project. Our advanced analytical tools provide speed, depth, and resolution. All profiling is coupled with our in-house antibody glycosylation assay, tailored to reveal structure-function relationships.
- We conductN-glycosylation profiling services for antibodies with high accuracy using intact mass spec for antibody glycosylation, capable of detecting even minor glycoform variants.
- For rapid timelines, our fully automated sample preparation for ultrafast N-glycosylation analysis of antibody therapeutics delivers data as fast as we can.
- We support both N-linked glycosylation antibody and O-glycosylated antibody detection, using orthogonal methods including HILIC-UPLC, MS, and lectin-based assays.
- Comparative profiling supports evaluation of cell culture impact on antibody N-glycosylation, ensuring consistency across batches and platforms.
- For in-depth investigations, we offer a full range of methods for glycosylation analysis of therapeutic antibodies, from MALDI-TOF MS to capillary electrophoresis.
Functional Validation
Ensuring glycoforms deliver intended biological activity is critical. Our functional validation assays help bridge structure to performance.
- Measure binding kinetics to Fcγ receptors and target antigens post-engineering with real-time biosensor tools.
- Assess effector function with ADCC/CDC assays in biologically relevant models.
- Evaluate tissue penetration and circulation time using in vivo models, validating glycosylation and its impact on the pharmacokinetics of monoclonal antibodies.
- Explore downstream applications like glycosylation antibody conjugation for targeted drug delivery or bispecific antibody design.
End-to-End Workflow for Antibody Glycosylation
A streamlined development path ensures smooth project progression from idea to validated antibody:
- Consultation — Define project goals and ideal glycoform profiles.
- Sample Submission — Send purified antibodies, supernatants, or cell lines.
- Glycoengineering — Modify expression systems or glycosylation machinery as needed.
- Glycan Profiling — Perform analytical assessments to quantify and verify glycans.
- Functional Testing — Correlate glycan structures with biological activity.
- Final Report Delivery — Receive a comprehensive report and optional expert consultation
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Therapeutic Uses of Antibody Glycoforms
- In oncology, we help design antibodies against glycosylated proteins in colorectal cancer that enhance tumor ADCC via hypersialylated Fc regions.
- Our platform enables glycosylation as a strategy to improve antibody-based therapeutics by enhancing half-life and receptor targeting.
- Anti-viral programs use glycan-optimized antibodies for improved mucosal stability and tissue penetration.
- Clients in autoimmunity leverage sialylated IgG variants for superior anti-inflammatory performance.
Why Partner With Creative Biolabs?
- Great Glycoform Precision with <5% variation across production batches.
- Over decades of expertise in Fc glycosylation antibody services.
- Supports both N-linked glycosylation antibody workflows and bispecific antibody formats.
- Suitable for IND-enabling studies and comparability assessments.
Related Services
In addition to antibody-focused solutions, Creative Biolabs provides a full spectrum of custom glycosylation services to support diverse biomolecule classes and therapeutic platforms. Our glycoengineering expertise extends far beyond antibodies:
- Custom Glycosylation of Proteins
- Custom Glycosylation of Peptides
- Custom Glycosylation of Cell Membranes
- Custom Glycosylation of Bacterial Membranes
- Custom Glycosylation of Small Molecules & Nucleic Acids
- Custom Glycosylation of Lipids
At Creative Biolabs, our custom glycosylation of antibodies service allows researchers to fine-tune therapeutic profiles, improving efficacy, safety, and manufacturability. Whether you're developing oncology antibodies, IVIG analogs, or novel bispecific constructs, we provide scalable, customizable glycoengineering solutions backed by decades of expertise. Contact us for further assistance with your project.
FAQs
Does glycosylation interfere with antigen binding?
Not when properly engineered. Our antibody glycosylation assay confirms that glycosylation sites are positioned away from the complementarity-determining regions (CDRs), preserving binding affinity and specificity.
How can we control high-mannose content like Man5?
By modulating pH, glucose, and oxygen in the culture environment, we can significantly reduce high-mannose glycoforms and achieve more human-like glycan profiles.
Can your platform detect both N- and O-glycosylation?
Yes. Our methods support both N-linked glycosylation antibody detection and O-glycosylated antibody detection using orthogonal approaches such as LC-MS/MS, CE, and lectin blotting.
How is glycosylation used to improve bispecific or conjugated antibodies?
We apply glycosylation antibody conjugation techniques for site-specific modification, enabling conjugation of payloads, oligonucleotides, or targeting moieties while preserving structural integrity.
References:
- Shade, Kai-Ting C., and Robert M. Anthony. "Antibody glycosylation and inflammation." Antibodies 2.3 (2013): 392-414. https://doi.org/10.3390/antib2030392
- Zlatina, Kristina, and Sebastian P. Galuska. "Immunoglobulin glycosylation–an unexploited potential for immunomodulatory strategies in farm animals." Frontiers in Immunology 12 (2021): 753294. https://doi.org/10.3389/fimmu.2021.753294
