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Rapid Antibody Glycoengineering in Chinese Hamster Ovary Cells
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Modulating antibody effector functions by Fc glycoengineering.

Mikel García-Alija1, Berre van Moer2, Diego E Sastre3

  • 1Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia 48903, Spain.

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|June 19, 2023
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Summary

Antibody glycoengineering aims to control therapeutic antibody glycoforms for enhanced efficacy and stability. Tailoring N-glycans on IgG antibodies optimizes their function in treating diseases like cancer and autoimmune conditions.

Keywords:
AntibodyEndoglycosidaseGlycoengineeringGlycosynthaseIgGN-glycosylation

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Area of Science:

  • Biopharmaceutical development
  • Glycobiology
  • Immunology

Background:

  • Therapeutic antibodies, particularly immunoglobulin G (IgG) monoclonal antibodies, are crucial for treating cancer, autoimmune, and infectious diseases.
  • Conserved N-glycosylation at Asn297 on IgG antibodies influences effector functions, complement activation, and antibody half-life.
  • Variations in N-glycans (fucosylation, galactosylation, sialylation, etc.) create distinct glycoforms with specific interactions with cellular receptors, impacting antibody function.

Purpose of the Study:

  • To explore strategies for producing therapeutic antibodies with specific, tailored glycoforms.
  • To enhance the efficacy, stability, and effector functions of antibody-based drugs through glycoengineering.
  • To address the challenge of inherent glycoform heterogeneity in clinically used antibodies.

Main Methods:

  • Review of antibody engineering strategies for glycoform control.
  • Discussion of glycoengineering approaches including engineered mammalian cell lines.
  • Inclusion of in vitro and in vivo glycoengineering techniques.

Main Results:

  • Antibodies are produced with a mixture of glycoforms impacting their therapeutic profile.
  • Specific glycoforms are linked to distinct functional outcomes and receptor interactions.
  • Tailored glycoforms offer potential for improved antibody-based therapeutics.

Conclusions:

  • Controlling antibody glycoforms is essential for optimizing therapeutic outcomes.
  • Advanced glycoengineering methods enable the production of homogeneous antibody glycoforms.
  • Targeted glycoengineering holds significant promise for the future of antibody-based therapies.