Therapeutic Fc Engineering Technology

Nowadays, therapeutic monoclonal antibodies have become an important treatment for cancer and autoimmune diseases. The efficacy of a monoclonal antibody not only depends on its antibody binding region (Fab), but its crystallizable region (Fc) also plays an important role. Fab can specifically recognize the tumor-associated antigen (TAA), thereby regulating the downstream signaling pathways related to TAA. Fc can exert a series of effect functions such as ADCC, ADCP and CDC to further enhance the efficacy of monoclonal antibodies. At the same time, Fc can also bind to FcRn to extend the half-life of monoclonal antibodies.

Although most therapeutic IgGs approved to date retain the natural IgG Fc domain, the knowledge gained in the past few decades provide opportunities for the design of tailored and more effective immunotherapies that exhibiting greater performance. The emergence of monoclonal antibodies for the treatment of various pathological conditions has provided more insights into the biology of Fc receptors and proposed new strategies for the development of improved therapies using Fc receptor interactions. Selecting the appropriate IgG subtype and Fc region modification strategies are becoming current a hot spot for therapeutic antibodies research and development.

Creative Biolabs always pays attention to the most cutting-edge research results and is committed to supporting researchers around the world. Keeping pace with the recent advances made in the design of biologics that modulate or exploit Fc receptor-IgG interactions, we provide customers with a variety of innovative Fc modification strategies, which are currently under investigation in clinical trials that have been precisely tuned to achieve a desired therapeutic effect.

Biological Function of Fc

The Fc region of IgG molecules can perform a series of biological functions to further enhance the efficacy of monoclonal antibodies. Fc can bind to FcγRs, which is mainly expressed on various types of immune leukocytes. When leukocytes are recruited and activated, they can trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP), thereby eliminating target tumor cells. Fc can also bind to serum complement molecules (C1q), and then form a membrane attack complex (MAC) to eliminate target cells. This process is called complement-dependent cytotoxicity (CDC). The Fc region can also bind to the newly born Fc receptor (FcRn) in a PH-dependent manner to prevent the antibody from being degraded by endosomes, thereby prolonging the half-life of the monoclonal antibody.

Schematic diagram of Fc region function: ADCC, ADCP, CDC. Fig.1 Schematic diagram of Fc region function: ADCC, ADCP, CDC.

Fc Modification Strategies

Fc modification achieves the enhancement of antibody function through directional design to meet the needs of different monoclonal antibodies. For example, increase the affinity of Fc and FcγRIIa/IIIa to enhance ADCC effect or increase the affinity of Fc and C1q to enhance CDC effect, thereby more effectively clearing target tumor cells; increase the affinity of Fc and FcγRIIb to enhance immunosuppressive effect, so it can be used for autoimmunity as well as the elimination of allergens; for simple antagonist antibodies, knocking out the binding of Fc and FcγRs can avoid side effects such as ADCC; enhancing the binding of Fc and FcRn can prolong the half-life of the monoclonal antibody in vivo.

Fc region modification strategies. Fig.2 Fc region modification strategies. (Sondermann, 2016)

For more details about our ADCC enhancement Therapeutic Fc Engineering Technology service, please do not hesitate to contact us.

Reference

  1. Sondermann, P., & Szymkowski, D. E. (2016). Harnessing Fc receptor biology in the design of therapeutic antibodies. Current Opinion in Immunology, 40, 78–87.

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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