Afuco™ Platform
The oligosaccharide from the amino acid asparagine-297 (N297), existing in the IgG
domain, is critical for the binding between FcγR and complement factor C1q. Currently,
several glycoengineered antibody treatments, anti-CD20 mAb and the
anti-CCR4 mAb, have been approved. Sufficient rationale is studied to
prove enhancing effect of glycoengineering-based ADCC. Creative Biolabs has established
an advanced Afuco™ platform for the glycoengineered therapeutic antibody production.
Fig.1 Our Afuco™
technology platform: Development of defucosylated antibody drugs by FUT8 gene knockout.
Using our DEFUCO™ platform, the de-fucose antibodies developed exhibit a significant
ADCC activity increase in vitro compared to unmodified antibodies:
● Platform
Instead of directly eliminating any genes, Creative Biolabs' proprietary technology redirects fucose synthesis through a heterologous enzyme, which could deplete
fucose pool inside the cell. For any successfully established stable CHO cell lines, it
could produce defucosylated antibodies with up to 100-fold ADCC activity against tumor
cells or other virus-infected cells.
We use for any novel antibody projects and biomarkers (ADCC enhanced originator
mAbs) or biosimilars projects if adjusting for specific fucose levels is critical.
● Fucoanalog™ Platform
On the contrary with genetic engineering at the cellular level, Creative Biolabs has
made a breakthrough in reducing or removing the fucose content on the antibody of
interest. This is achieved by adding a fucose analog to the medium to regulate the
metabolic pathway of the cell. A significant increase in the activity of the monoclonal
antibody ADCC is therefore achieved.
Fc Protein-Engineering Platform
The rationale for developing Fc protein-engineered ADCC is to swap amino acids directly
in the FcγR / FcγRIIIa binding site within the Fc domain of that antibody. For example,
modifactions on the following five sites of anti-HER2 monoclonal antibody, F243L/R292P/Y300L/L235V/P396L
in the Fc region, can reduce its binding ability to CD32B and hence, improve the ADCC
effect. By exchanging all solvent amino acids in the human IgG1 Fc domain with alanine,
our approach can identify various Fc domain variants with different FcγR / FcγRIIIa binding
profiles. Using this approach, we identified a triple variant that shows a high affinity
for FcγR / FcγRIIIa and thus, stronger ADCC activity.
Cross-Isotype Engineering
Creative Biolabs developed a “cross-isotype” Fc domain – IgGA, using advanced protein
engineering strategies to produce ADCC-enhanced antibodies via a hybrid IgG1/IgA Fc
domain. These engineered IgGA antibodies can significantly increase FcγRIIIa (CD16a)
binding capacity. In vitro and animal experiments have shown that IgA exerts an
efficient and stronger cell-killing effect than IgG1, who goes through the FcαRI
receptor by the surface of effector cells.
CD16A Bispecific Antibody Engineering
Creative Biolabs’ ADCC antibody development team provides a novel way to target NK and
DC cells through high-affinity CD16A bispecific antibodies, and then driving activated
NK/DC cells to exert ADCC effects on tumor cells. A kind notice that our antibody
customization team would be able to help you design and co-develop CD16A bispecific
antibodies, specifically in combination with other highly expressed antigens on the
surface of tumor cells, such as BCMA (B-cell maturation antigen), etc. A variety of published studies have
demonstrated that CD16A bispecific antibodies (BiAbs) with enhanced ADCC modification have better in vitro killing effects.
Glyco- and Fc Protein Dual Engineering
ADCC-optimized amino acid exchanged Fc variants, when working with glycoengineered
engineered variants, show improved NK cell-mediated ADCC activity. Creative Biolabs’
scientists have developed combined Fc engineering approaches based on the latest
research. We are committed to achieving greater success with you together.
For more details about our ADCC enhancement technology service, please do not hesitate to contact us.
Reference
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Rodríguez-Nava, Cynthia, et al. "Mechanisms of action and limitations of monoclonal antibodies and single chain fragment variable (scFv) in the treatment of cancer." Biomedicines 11.6 (2023): 1610.
under Open Access License CC BY 4.0. The original image was modified by extracting and using a part, and certain words were hidden from this image.
