Fc Engineering Service for Aglycosylation

Antibodies and antibody-based drugs are currently the fastest growing therapies. In the past thirty years, more than 30 therapeutic monoclonal antibodies and their derivatives have been approved, and they have been successfully used in various indications, including cancer, organ transplantation, autoimmune/inflammatory diseases and cardiovascular diseases. The isotype of choice for antibody therapeutics is human IgG, whose Fc region contains the ubiquitous asparagine residue (N297), which serves as the receptor site for N-linked glycans. This glycosylation has a great influence on the activity of IgG. The properties of these glycans can decisively affect the therapeutic performance of recombinant antibodies, and their deletion or Engineering can lead to loss of Fc effector function, greater immunogenicity and unfavorable pharmacokinetic characteristics.

Recent studies have shown that aglycosylation can be genetically engineered for glycosylation antibodies to have novel or enhanced effector functions and retain good pharmacokinetic properties. The currently marketed Roche anti-PD-L1 monoclonal antibody Atezolizumab uses IgG1 (N297A) to remove glycosylation. There is also a series of monoclonal antibodies modified with N297A in clinical trials. Therefore, extensive engineering of non-glycosylated Fc has transformed aglycosylated IgG antibodies into a new class of effector functional human immunotherapeutics.

Aglycosylated Antibodies Under Clinical Trials

Multiple mAbs with various modifications in the Fc region are being studied in different phases of clinical trials, plesae refer to Figure 1. These molecules can be roughly divided into three categories: (1) enhanced effector responses can treat cancer and infectious diseases; (2) can inhibit immune activation to treat inflammatory diseases; (3) new aglycosylated monoclonal antibodies, with inert or active immune function.

Fc-engineered antibody candidates under clinical evaluation. Fig.1 Fc-engineered antibody candidates under clinical evaluation. (Saxena, 2016)

Key Features of Aglycosylated Antibodies

Features of glycosylated and aglycosylated antibodies. Fig.2 Features of glycosylated and aglycosylated antibodies. (Ju, 2014)

Our Capabilities

Creative Biolabs provides a variety of glycosylation modification technologies to therapeutic antibodies, including fucose deletion, sialylation, fucose removal and sialylated antibody modification. At the same time, we provide customers with customized antibody glycosylation design and services, and assist in the development of novel antibodies and high-end biobetter antibodies.

According to the different needs of customers for antibody characteristics, we provide corresponding glycosylation services, including but not limited to

For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

  1. Saxena, A., & Wu, D. (2016). Advances in therapeutic Fc engineering–modulation of IgG-associated effector functions and serum half-life. Frontiers in immunology, 7, 580.
  2. Ju, M. S., & Jung, S. T. (2014). Aglycosylated full-length IgG antibodies: steps toward next-generation immunotherapeutics. Current opinion in biotechnology, 30, 128-139.

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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