Direct-targeting monoclonal antibodies (mAbs) approved for usage in oncology mainly belong to the immunoglobulin (Ig) G class currently. In fact, non-IgG therapeutic antibodies come of age with major progress in different kinds of human diseases, such as cancers and chronic inflammation. IgG mAb is no longer the only player in the therapeutic fields owing to antibody engineering technique, which is further driving the development of novel antibody formats. Besides, genetically modified cell-based therapies that harness the power of the immune system, together with non-IgG therapeutic antibodies, have improved cures in intractable human diseases. As an acknowledged antibody service provider, Creative Biolabs now offers various non-IgG therapeutic antibody engineering services to help our customers obtain ideal results and promote their research and projects successfully.
Distributed under CC BY-SA 4.0, from Wiki, without modification.
Chimeric antibodies are modified antibodies that combine the antigen-binding regions of one species with the constant domains of another to reduce immunogenicity. A key early use was transforming mouse monoclonal antibodies into mouse-human chimeric antibodies, retaining antigen specificity while enhancing compatibility. These antibodies offer advantages over original ones, including longer half-life, reduced immunogenicity, and improved complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Since the introduction of this technology in 1984, the FDA has approved several chimeric antibody drugs, such as Infliximab, Cetuximab, and Abciximab, which are all IgG isotypes used to treat inflammation, autoimmune diseases, and tumors. To address the limitations of non-human antibodies, Creative Biolabs applies recombinant technology to create non-IgG chimeric antibodies.
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Chimeric IgA Antibody Engineering Service | |
Chimeric IgM Antibody Engineering Service | Engineered IgM/IgG Chimeric Antibody |
Chimeric IgE Antibody Engineering Service |
Schematic diagram of
chimeric antibody construction1
Antibody humanization is essential for reducing immunogenicity, improving pharmacokinetics, and preserving the affinity and specificity of therapeutic monoclonal antibodies (mAbs) derived from non-human systems. Techniques such as complementarity determining the region (CDR) grafting, chain shuffling, and resurfacing are commonly used for this purpose. As non-IgG antibodies like IgA, IgM, and IgE gain importance in diagnosis and treatment, Creative Biolabs offers advanced humanization services. Using recombinant DNA technologies, we optimize non-IgG antibodies by inserting CDR segments into human frameworks, enhancing their therapeutic potential.
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Antibody Humanization Design |
Vector Synthesis and Cloning |
Transient Expression |
Stable Expression of Cell Lines |
Glycosylation, a post-translational modification, involves attaching glycan sugars to proteins, lipids, or other molecules through enzymatic processes in the Golgi apparatus and endoplasmic reticulum. The two primary types are O-linked and N-linked glycosylation, contributing to protein diversity and influencing molecular activity. Therapeutic antibodies benefit from glycosylation modifications, especially in the Fc and sometimes Fab regions, enhancing functions such as stability, safety, and efficacy. While most glycoengineering efforts focus on IgG antibodies, non-IgG antibodies like IgA, IgM, and IgE possess unique glycosylation sites, with more glycan sites than IgG. Developing glycosylated non-IgG antibodies is essential for improving their therapeutic performance and expanding their clinical potential.
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IgA Glycosylation Service | Antibody GlycoOpitimize Platform |
IgM Glycosylation Service | |
IgE Glycosylation Service |
Bispecific antibodies (BsAbs) are specialized antibodies capable of binding two different targets simultaneously, such as antigens, receptors, or cells. BsAbs come in various formats, including IgG-like (with Fc regions) and non-IgG-like structures. They are widely used in diagnosis, drug delivery, and therapy, particularly in cancer immunotherapy, due to their ability to link cytotoxic cells with specific targets for enhanced therapeutic effects. Several BsAbs have been approved for cancer treatment, with many others in clinical trials. Creative Biolabs focuses on advancing non-IgG BsAbs, leveraging the unique properties of antibodies like IgA, IgM, and IgE, such as mucosal immunity and complement activation. This strategy addresses a gap, as most BsAbs in clinical use are based on IgG isotypes. By integrating BsAbs with non-IgG antibodies, Creative Biolabs aims to optimize therapeutic performance and expand treatment possibilities.
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BsAb Design | Target Binding |
Isotype Selection | |
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Optimization to Improve Properties | Half-life |
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Production in Quantities | Recombinant DNA Technology |
Hybrid-Hybridoma Technology | |
Isotype Converting | |
Conjugation |
Half-life refers to the time required to eliminate 50% of an antibody from the body, impacting the dosage and frequency of therapeutic agents. Prolonging antibody half-life improves efficacy, reduces treatment cycles, and lowers costs, which are critical in the growing therapeutic antibody market. Both IgG and non-IgG antibodies show species-specificity in target binding and stability, with Fc regions playing a crucial role in long-term stability. However, non-IgG antibodies lack binding sites for FcRn, limiting their half-life. Solutions such as glycoengineering, albumin fusion, and constructing hybrid antibodies can extend non-IgG antibody retention, enhancing their pharmacokinetics and therapeutic potential. Creative Biolabs leverages these strategies to develop functional non-IgG antibodies with improved exposure and efficacy.
Selecting the appropriate antibody isotype is crucial for effective therapies, as different immunoglobulins (IgG, IgA, IgE, IgM, and IgD) play distinct roles in immune responses. Class switching occurs naturally when B cells transition from producing IgM to other isotypes, with the variable region of the antibody remaining unchanged to retain antigen specificity. This switch allows antibodies to engage different immune mechanisms, enhancing their ability to combat pathogens. In vitro, class-switch recombination (CSR) involves modifying the constant region of the heavy chain through DNA recombination processes initiated by activation-induced cytidine deaminase. Aided by antibody engineering techniques, we provide isotype switching services among the IgG, IgA, IgE, and IgM isotypes.
Fig.2 Class switch recombination. Distributed under Public domain, from Wiki, without modification.
Antibody-drug conjugates (ADCs) are advanced biopharmaceuticals that combine mAbs with cytotoxic agents to target cancer cells while minimizing harm to healthy tissue. Traditional chemotherapy drugs, with low selectivity, damage both tumor and normal cells, and many approved antibody therapies require combination with chemical drugs. ADCs address this by attaching cytotoxic agents to human or humanized mAbs through chemical linkers, ensuring targeted delivery of the drug within cancer cells. Despite the growing interest in ADCs, current developments focus exclusively on IgG antibodies, overlooking the unique therapeutic potential of non-IgG antibodies due to production challenges. Creative Biolabs offers comprehensive design and development services for non-IgG ADCs, aiming to unlock new therapeutic possibilities beyond traditional IgG-based platforms.
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Non-IgG ADC design | |
Linker and Conjugation Services | Linkers Synthesis |
Linkers Modification | |
Assembly | |
Evaluation Services | In Vitro Evaluation |
In Vivo Evaluation |
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A: Non-IgG antibodies, such as IgA, IgM, and IgE, have emerged as essential tools for treating complex human diseases like cancer and chronic inflammation. These antibodies possess unique properties, including distinct glycosylation patterns, mucosal immunity and complement activation, making them valuable alternatives to traditional IgG antibodies.
A: Glycosylation, a post-translational modification, enhances the stability, safety, and efficacy of non-IgG antibodies. Non-IgG antibodies contain unique glycosylation sites, offering distinct therapeutic advantages. Adjusting glycosylation patterns through engineering can significantly improve antibody functionality and clinical outcomes.
A: Bispecific non-IgG antibodies can simultaneously bind to two distinct targets, such as antigens or receptors, facilitating enhanced therapeutic effects. These antibodies are particularly useful in cancer immunotherapy, as they bridge cytotoxic cells with specific targets. Non-IgG bispecific formats leverage the unique immune properties of antibodies like IgA and IgM, expanding therapeutic options beyond traditional IgG-based antibodies.
A: Humanization of non-IgG antibodies minimizes immune responses in humans by grafting key antigen-binding regions onto human frameworks. This process maintains antibody specificity and improves pharmacokinetics, enabling safer and more effective treatments. Humanized non-IgG antibodies, like those based on IgA, IgM, and IgE, are increasingly being applied in diagnostics and therapies.
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