Dual ADCC/CDC Enhancement Technology

Dual-ADCC/CDC-Enhancement-Technology

Dual ADCC/CDC Enhancement Technology

Intending to improve antibody therapeutic activity in human applications, scientists focus on effector functions, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Instead of modifying ADCC/CDC functions separately, one of the pioneering methods is to incorporate multiple enhancement modifications into one antibody platform to overcome multiple complications and clinical resistance brought by tumor progress. We believe dual ADCC and CDC enhanced antibodies are a promising combination to the third-generation antibody therapeutics.

Powered by our professional team and their advanced knowledge on ADCC / CDC enhancement technology, Creative Biolabs is dedicated to the design and development of dual ADCC / CDC enhanced antibodies—two key engines for therapeutic antibodies. Our proprietary dual ADCC/CDC⁺ antibody platforms hopefully create superior therapeutic antibody with enhanced ADCC and CDC activity.

ADCC/CDC Mechanism

In ADCC, an Fcγ receptor (FcγR or FCGR) on the surface of an immune effector cell binds to a specialized Fc region of an antibody, which triggers the activation of effector cells and the secretion of various substances (lyase, perforin, granzyme, TNF) that may later mediate target cell destruction. In CDC, C1q binds to antibodies that can trigger the complement cascade and formation of membrane attack complexes (MAC) (C5b to C9) on the surface of target cells, leading to activation of classical pathway complement. Both of these mechanisms are highly dependent on the glycoprotein and protein structure in Fc region and the activation mechanism of the complement system. Two above features will be the primary focus of our dual ADCC/CDC enhancement techniques.

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Versatile Platforms

Duboom™ Platform
Crosstype™ Platform
Glyco- and Fc Protein Dual Engineering

Duboom™ Platform

Creative Biolabs has already established an advanced dual ADCC/CDC⁺ enhanced antibody platform—Duboom™, for the production of ADCC/CDC⁺ products. The Duboom™ platform is a integration of the Afuco™ platform with the Crea-Tag™ technology platform. The finished product, dual ADCC/CDC⁺ antibody, gives a successful combination—fucose depletion on Fc-linked oligosaccharides for ADCC enhanced modification and Crea-Tag™ protein-based complement modification to enhane CDC.

Mechanism of action (MOA) of the combination:

  • Afuco™ platform is under development because non-fucosylated modified antibodies exhibite significant ADCC enhancing effects.
  • Crea-Tag™ protein as a fusion protein, when coexpresseing with other antibody, can dispalce the complement factor H (CFH) on tumor cells and activate complement-mediated lysis.

Duboom™ platformFig.1 Duboom™ platform.

Crosstype™ Platform

In vitro and animal experiments have shown that IgA exerts a more efficient and stronger cell-killing effect than IgG1 through the FcaRI receptor on the surface of effector cells. From this, Creative Biolabs proposes a unique tandem IgG1 / IgA2 antibody that can retain IgGl FcγR binding and FcRn mediated serum persistence with enhanced cytotoxicity.

IgG1/IgA2 tandem Fc fusion design and SPR anlaysisFig.2 IgG1/IgA2 tandem Fc fusion design and SPR anlaysis.

Glyco- and Fc Protein Dual Engineering

CDC-optimized amino acid exchange-induced Fc variants, when working together with glycoengineered dual engineered variants, show improved NK cell-mediated ADCC and CDC activity. Creative Biolabs’ scientists have developed combined approaches based on these latest research and findings. We are committed to combining our expertise with your mastery to achieve great success.

An Fc dual engineered CD20 antibody has enhanced ability to trigger CDC and ADCC. The following figure shows the dose-dependent induction of CDC (middle panel ) and ADCC (right panel) against GRANTA-519 cells by rituximab variants.Fig.3 An Fc dual engineered CD20 antibody has enhanced ability to trigger CDC and ADCC. The following figure shows the dose-dependent induction of CDC (middle panel) and ADCC (right panel) against GRANTA-519 cells by rituximab variants.

Feature of dual ADCC/CDC platform

Creative Biolabs’ dual ADCC/CDC platform creates opportunities to enhance the intrinsic killing power of therapeutic antibodies:

  • Suitable for multiple antibodies against different targets
  • Inspiring potential for new or improved treatments for a variety of indications
  • Can be combined with other antibody technologies for maximum effect

For more details about our Dual ADCC/CDC Enhancement Technology service, please do not hesitate to contact us.

References

  1. Borrok MJ.; et al. Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with FcαRI (CD89) binding. mAbs. 2015, 7(4):743-751.
  2. 2. Wirt T.; et al. An Fc Double-Engineered CD20 Antibody with Enhanced Ability to Trigger Complement-Dependent Cytotoxicity and Antibody-Dependent Cell-Mediated Cytotoxicity. Transfusion Medicine and Hemotherapy. 2017, 44(5):292-300.

RESOURCES

Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details. 

All products and services are for Research Use Only. Do Not use in humans.

CASE STUDY

ADCC Assay WT vs AfucoTM Mabs  Visit

Resource

Antibody Fc Engineering: Towards Better Therapeutics  Visit

ONLINE INQUIRY

Creative Biolabs has established a team of customer support scientists ready to discuss ADCC/CDC optimization strategies, antibody production, bioinformatics analysis and other molecular biology/biotechnology issues.

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