Fc Engineering is Significant for Therapeutic Antibody Development.
Monoclonal antibodies have emerged as a highly effective therapeutic option in various disease areas, offering targeted treatment with minimal side effects. One exciting advancement in monoclonal antibody therapy is Fc engineering, which involves modifying the Fc region of the antibody to enhance its therapeutic potential. This technology allows for improved binding to specific receptors, leading to enhanced antibody functions such as ADCC and CDC. By leveraging Fc engineering, customers can optimize the efficacy and safety of monoclonal antibodies, making them more valuable in treating numerous medical conditions.
Fig.1 Overview of the important functions of therapeutic antibodies currently in use.1, 3
Our Fc Engineering Services
Creative Biolabs focuses on the critical importance of Fc engineering in enhancing the effectiveness of monoclonal antibodies across various disease treatments. Our extensive portfolio of Fc engineering services ranging from molecular to apparent modification is tailored to meet diverse research needs. With our cutting-edge technology platforms and wealth of antibody engineering experience, we are well-equipped to deliver impactful outcomes and detailed reports promptly.
In addition, Creative Biolabs offers a diverse range of techniques for Fc engineering that are designed to enhance antibody characteristics and functions, which include:
Our skeleton engineering involves amino acid substitutions at the Fcγ receptor binding site within the Fc domain of the antibody, as well as swapping larger amino acid sequences between isotypes. This process allows for the creation of variant antibodies with modified Fcγ receptor binding profiles, which can be selected for optimal characteristics based on specific requirements. Our antibody skeleton engineering services include:
| Amino Acid Substitution |
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| Our approach combines computer modeling with screening techniques to pinpoint specific amino acid changes that can enhance the activity of FcγR receptors in immune cells. |
| Exchanging Larger Amino Acid Stretches Between Different Isotypes |
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| Through computational modeling and advanced biological techniques, we exchange amino acid extensions between antibody isotypes to achieve a combination of effector functions typically found in different isotypes. |
IgG antibodies showcase a pivotal N-glycosylation site on the Fc region where a sophisticated, biantennary glycan is appended. The intricate makeup of this glycan directs antibody effector functions by influencing the Fc's affinity towards Fc receptors. Additionally, glycosylation stands as a crucial factor in shaping the properties of antibody drugs, such as immunogenicity and duration of effectiveness. Creative Biolabs provides a comprehensive strategy for regulating glycan composition, thereby optimizing the safety and efficacy of antibody-based therapeutics. Our Fc glycoengineering services involve:
| Antibody Glycosylation Analysis |
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| Our specialized techniques in chromatography and mass spectrometry allow for in-depth analysis of antibody glycosylation, providing detailed information on glycosylation types, sites, components, and more. |
| Host Cell Glycoengineering |
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| Creative Biolabs provides a wide selection of host cell expression systems that can be tailored to suit the specific glycosylation requirements of each biotherapeutic product. Our experts help recommend the most suitable cell line and culture conditions to achieve the desired glycosylation pattern, ensuring optimal efficacy and safety of the final product. |
| Antibody Afucosylation for Enhanced ADCC |
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| We utilize various methods to disable fucosylation and eliminate fucose to create high-potency non-fucosylated therapeutic antibodies, which demonstrate enhanced effectiveness in vitro and in vivo compared to fucosylated versions. |
| Optimization of Sialylation |
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| Leveraging our Antibody GlycoOptimize™ Platform, we offer cell line development services designed to produce optimized sialylated recombinant Fc as a reliable IVIg alternative for anti-inflammatory applications, ensuring optimized IgG sialylation under controlled conditions. |
| Fully Human Glycosylation |
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| Human cell lines offer a promising alternative to non-human hosts, enabling the production of recombinant antibodies with fully human glycosylation patterns. This reduces downstream processing costs and minimizes immunogenic risks from non-human glycans. Creative Biolabs utilizes these cell lines in our platform to produce high-yield therapeutic antibodies, optimizing their therapeutic efficacy and bioavailability. |
| Antibody GlycoOpitimize™ Platform |
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| Creative Biolabs has developed an extensive Antibody GlycoOpitimize™ Platform that delves into gene, cell, and metabolic aspects to enhance the understanding of glycosylation's role in biology and function. This platform also works towards optimizing antibody therapeutic activities for improved efficacy and safety. |
| Optimization of Galactosylation and Degree of Branching |
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| Our tailored expression systems and carefully calibrated culture media help produce antibodies with ideal galactosylation levels and optimal branching, thereby enhancing drug effectiveness. Additionally, our services serve as a valuable resource in understanding the correlation between glycosylation status and antibody functionality and efficacy. |
Our Fc engineering services deliver for global customers plenty of benefits as follows:
Engineering Approach: Amino acid substitution
Description: This study focused on enhancing the pharmacokinetics of a pH Toggle switch Fc variant through the introduction of the L309D/Q311H/N434S (DHS) substitutions. The new variant showed significantly improved half-life compared to both native IgG1 and commonly used half-life extension variants, in both hFcRn transgenic mice and newly developed knock-in mouse models.
Fig.2 Key attributes of DHS Fc variants for consideration in therapeutic antibody development.2, 3
Q1: Are Fc-engineered antibodies approved for clinical use?
A1: Modified Fc region of therapeutic antibodies with improved effector functions, extended half-life, or reduced immunogenicity, currently in advanced stages of clinical development or already authorized for use in patients.
Q2: How can antibody sequencing engineering be used at the Fc site?
A2: Therapeutic antibodies are designed with specific modifications at the Fc site using precise genetic engineering methods after obtaining the heavy and light chain sequences. This approach allows for structure-based sequence engineering to enhance antibody functionality. Alternatively, large phage or yeast display libraries can be generated to identify the most optimal Fc variant through empirical-based sequence engineering methods.
With decades of experience in antibody development, we are dedicated to offering high-quality custom-specific antibody Fc engineering services. Our expert academic teams leverage their industry knowledge and regulatory expertise to deliver cutting-edge solutions to global customers. Get in touch with us now or fill out an inquiry form to discover how we can assist you with your antibody engineering requirements.
References
For Research Use Only.
