How are afucosylated antibodies developed?

Afucosylated antibodies are recombinant antibodies that lack fucose, a sugar molecule, on their Fc region. This structural modification significantly enhances antibody-dependent cellular cytotoxicity (ADCC), making them a key tool in oncology and other areas where potent immune cell engagement is required.

This article explains how afucosylated antibodies are produced, which methods are used to remove or block fucosylation, and why this modification matters for biopharmaceutical development.

Why are afucosylated antibodies developed?

Afucosylation of antibodies offers distinct advantages, primarily enhancing their ability to engage with the immune system. By removing fucose, afucosylated antibodies exhibit heightened antibody-dependent cellular cytotoxicity (ADCC).

This modification augments their capacity to bind more efficiently to immune cells, potentially leading to increased destruction of targeted cells or pathogens. Consequently, afucosylated antibodies hold the promise of significantly bolstering therapeutic efficacy, paving the way for more potent and targeted treatments against various diseases.

Developing afucosylated antibodies – basic principles

Creating afucosylated antibodies involves altering their structure by targeting the sugar components within the Fc region. This modification primarily focuses on reducing or eliminating fucose residues.

Read more: Applications of afucosylated antibodies

Scientists employ genetic engineering, enzymatic modification, or glycoengineering techniques to achieve this alteration. The goal is to manipulate the glycan structure to minimize fucose content, enhancing the antibodies’ functional properties.

Methods in afucosylated antibody development

There are different, very specific methods in afucosylated antibody development, some of which are listed below:

• GDP-fucose control: Utilizing enzymes involved in the biosynthesis of GDP-fucose, a critical precursor for fucosylation, to modulate the fucosylation process.
• FUT8: Manipulating the activity of the FUT8 gene, responsible for a specific enzyme adding fucose to antibodies
• SLC35C1 modifications: Targeting the transporter gene SLC35C1 to regulate fucosylation in the Golgi apparatus.
• Bisecting GlcNac generation: Introducing modifications in the glycan structures of antibodies by increasing bisecting GlcNAc formation, impacting fucosylation patterns.
• Bacterial RMD expression in CHO cell cytosol: Disrupting the de novo pathway of GDP-fucose by expressing bacterial RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase) in the cytosol of Chinese Hamster Ovary (CHO) cells.
• Fucosylation inhibition with biohemicals: Employing specific inhibitors that hinder the fucosylation process within cells.
• Plant cell expression platforms: Leveraging plant cells as alternative platforms for the production of antibodies with modified glycosylation patterns.
• Chemoenzymatic remodeling: Using a combination of chemical and enzymatic methods to selectively modify glycan structures of antibodies, allowing controlled fucosylation alterations.^​1​

Afucosylated antibodies by evitria – afucosylation with GlymaxX® technology

evitria, in an exclusive partnership with ProBioGen’s GlymaxX® technology, offers high quality expression of afucosylated antibodies. Engineered for heightened Antibody-Dependent Cellular Cytotoxicity (ADCC), these antibodies demonstrate superior efficacy against tumorigenic and infected cells.

evitria’s approach, avoiding Fc mutations, ensures equivalent yields and stability to native antibodies with reduced immunogenic risks. Specializing in recombinant antibody production, evitria guarantees swift, high-quality results of afucosylated antibody expression. From sequence to antibody in just five weeks, evitria’s commitment is to timely support partners worldwide with high-quality afucosylated antibodies.

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