Crea-Tag™ Platform
Creative Biolabs already developed a Crea-Tag™ protein that can be co-expressed as the fusion protein.
By displacing the complement factor H on tumor cells, together they can activate complement-mediated
lysis.
Highlighted Functions of Factor H:
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Factor H is the primary soluble regulator at the alternative complement pathway.
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Factor H binds to host cells via the non-covalent interaction with membrane polyanions, C3b, and its
fragments, protecting them from complement attack.
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Factor H is responsible for inhibiting the alternative pathway CDC and blocking its activity.
Fig.1 Mode-of-action: Crea-Tag™ displaces
the CFH (Complement Factor H) on tumor cells.
Fc Protein Engineering Platform
Almost identical to the process of optimizing ADCC activity, an engineered Fc protein backbone is used
to improve the ability of IgGl antibodies to trigger CDC. Also, it is known that some key amino acids of
the complement component C1q can bind to the CH2 domain of IgG1. Creative Biolabs proposes the exchange
of all solvent amino acids in the human IgGl Fc domain and alanine can identify various Fc domain
variants with increased C1q binding properties. Because of this, we offer a triple variant with a higher
C1q binding capacity and stronger CDC activity.
Fig.2 Subcutaneous tumor development was investigated in vivo in a severe combined immunodeficiency (SCID) xenograft model.2
Crosstype™ Engineering Platform
Creative Biolabs has already established an advanced CDC-enhanced antibody platform—Crosstype™, for the
production of Fc engineered therapeutic antibodies. Crosstype™ allows our CDC⁺ antibody Fc region to
exhibit a greater binding capacity to C1q while ADCC activity remains unaffected.
The current methods to enhance CDC effect include:
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Modification of the Fc region to increase its binding capacity to C1q
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Modification of the IgG3 hinge region to increase its binding capacity to C1q
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Construction of an IgG subtype (cross-subtype) to increase overall binding capacity
Because antibody-mediated CDC activity is heavily influenced by its subtype, our Crosstype™ platform is
based on the IgG1/3 subtype cross-subtype technology, which screens various combinations of
CH1-hinge-CH2-CH3 while comprehensively evaluateing CDC activity.
Fig.4 Schematic diagram of IgG1/3
cross-subtype.
Highlighted Functions for Engineered Fc Regions:
• Increased CDC function
We are committed to the development of CDC⁺ therapeutic antibodies and hopefully, increasing
effector function to improve the therapeutic activities of antibodies.
• Extended half-life
Increasing serum persistence is the key to increase antibody efficacy. The increased half-life
allows for higher circulating levels, lower frequency administration and reduced dose during
experiements.
For more details about our CDC Enhancement Technology service, please do not hesitate to contact us.
References
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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.
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de Jong, Rob N., et al. "A novel platform for the potentiation of therapeutic antibodies based on antigen-dependent formation of IgG hexamers at the cell surface." PLoS biology 14.1 (2016): e1002344.
under Open Access License CC BY 4.0 The original image was modified by extracting and using a part, and the title was changed to “ Subcutaneous tumor development was investigated in vivo in a severe combined immunodeficiency (SCID) xenograft model ”
