Since the commercial development of therapeutic monoclonal antibodies commenced in the early 1980s, the monoclonal antibodies have grown to become the most successful class of biotech drugs for the diagnosis and treatment against various diseases and infections. Besides the traditional IgG antibody, Creative Biolabs can help to develop Non-IgG therapeutic antibodies for our customers all over the world.
Immunoglobulins Introduction
In general, distinguished by the type of heavy chains in the molecule, there are five primary classes of immunoglobulins (Ig), which are IgG, IgM, IgA, IgD, and IgE. IgG molecules have heavy chains known as γ-chains; IgMs have μ-chains; IgAs have α-chains; IgEs have ε-chains; and IgDs have δ-chains. The different heavy chain polypeptides result in different functions in immune responses. IgG is the most predominant Ig class present in human serum. IgA monomeric molecular consists of two identical heavy chains (HC) and two light chains (LC) polypeptides. Two identical HC and two LC polypeptides are assembled into higher polymers of IgM molecular, such as pentamer and hexamer. IgE heavy chain has a total of 4 constant domains and 1 variable domain, and the light chain contains 1 variable and 1 constant domain. Properties and specific comparison of these five antibody isotypes are generally listed in table 1. As a senior service provider, Creative Biolabs has accumulated over 10 years' experience and acquired reputations in antibody development. Based on possessing experience and well-established platforms, we have successfully constructed a novel service system to provide comprehensive non-IgG therapeutic antibodies development services, which include but are not limited to:
Fig.1 IgG, IgE, IgD, IgM, and IgA schematic
representations.
Table 1 Comparison of five antibodies. (Panawala, 2017)
| The Five Immunoglobulin (Ig) Isotypes | ||||||
| IgG | IgM | IgA | IgE | IgD | ||
| Structure |
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| Heavy Chains | γ (gamma) | μ (mu) | α (alpha) | ε (epsilon) | δ (delta) | |
| Antigen binding sites | 2 | 10 | 4 | 2 | 2 | |
| Molecular weight | 150 kDa | 900 kDa | 385 kDa | 200 kDa | 180 kDa | |
| Subclasses | IgG1, IgG2, IgG3 and IgG4 | — | IgA1 and IgA2 | — | — | |
| Percentage of total antibody in serum | 80% | 6% | 13% | 0.002% | 1% | |
| Distribution | Intravascular and extravascular | Mainly intravascular | Mainly in mucosal areas, also in saliva, tears, breast milk, intravascular and secretions. | Basophils and mast cells (in saliva and nasal secretions) | Lymphocyte surface | |
| Receptors | FcγRn and FcRn | FcμR, Fcα/μR, pIgR | FcαRI, Fcα/μR, pIgR | FcεRI and FcεRII | IgD B-cell receptor | |
| Crosses placenta | √ | X | X | X | X | |
| Fixes complement | √ | √ | X | X | X | |
| Fc binds to | Phagocytes, monocytes, macrophages, dendritic cells, etc. | Mesangial cells and macrophages | Monocytes, macrophages, neutrophils, and eosinophils | Mast cells and basophils | Basophils and mast cells | |
| Half-life | ~21 days (IgG3: 7 days) | ~5-6 days | ~5-6 days | ~2 days | ~2.8 days | |
| Properties | The most prevalent antibody in serum, also the only antibody able to cross the placenta (except IgG2). | The largest antibody, also the first human immunoglobulin. | The most abundant antibody class in secretions. | The least abundant isotype in the serum, can’t activate the complement system. | < 1% of the total antibodies in the blood, co-expressed with IgM on the B cells. | |
| Functions | Main blood antibody of the secondary immune response, neutralizes toxins, opsonization. | The main antibody of the primary immune response, best at fixing complement; the monomer form of IgM serves as the B cell receptor. | Secreted into mucus, tears, saliva, colostrum to function in mucosal immunity. | The antibody of allergy and anti-parasitic activity. | Unknown | |
Since the first therapeutic monoclonal antibody was approved by the Food and Drug Administration, more and more monoclonal antibodies have made enormous contributions to the treatment of human disorders. In addition to these well-developed IgG monoclonal antibodies, scientists in Creative Biolabs found that non-IgG (mainly IgA, IgM, and IgE) antibodies also have shown good performances in some diseases diagnosis and therapies. Therefore, we have set up a special scientific team to provide therapeutic non-IgG antibody discovery services for our global clients.
Antibody has made a pivotal contribution to the human disease treatment and health with the development of updated antibody biotechnology, among which antibody engineering is an indispensable method to optimize the performance of antibodies. In Creative Biolabs, not only IgG antibodies, but also non-IgG antibodies (mainly IgA, IgM, and IgE) are well developed. Our professional scientists optimize non-IgG antibodies to obtain better efficacy by innovative engineering technologies, such as humanization, glycosylation, conjugation.
The classical process of antibody production is the hybridoma technique through fusing antibody-secreting spleen cells from animals immunized by purified antigen with an immortal myeloma cell. Besides hybridoma technologies, several novel antibody preparation methods have been developed recently, such as phage display, single B-cell amplification. Once the sequence is provided, scientists can start with gene synthesis and plasmid construction. According to the subsequent transient transfection and stable cell culture, the antibody can be obtained. An antibody with high specificity and purity is the basis of experimental immunology technology as well as the key factor of the success of the scientific experiments. In order to get the purified antibodies, the corresponding purification methods must be performed including protein A/G affinity chromatography, ion-exchange chromatography, and size-exclusion chromatography.
Due to their different characteristics, the production and purification methods of non-IgG antibodies are different and even more difficult than those conventional antibody production and purification technologies. These difficulties are also some of the critical factors hindering the development of non-IgG antibodies. It is excited that Creative Biolabs is the one who is capable to support our clients in non-IgG antibodies production and purification using our abundant experience and expertise in this field.
Antibody characterization is an important process to generate an antibody with dependable, predictable, and intended performance. Creative Biolabs has developed several technologies to evaluate the quality, quantity, and function of the produced non-IgG therapeutic antibodies, such as enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunoblotting, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), high-performance liquid chromatography, mass spectrometry, etc.
The PK/PD (Pharmacokinetic/Pharmacodynamics) properties of monoclonal antibodies (mAbs) are quite complex compared with other small molecules. PK/PD characteristics of mAbs mainly include exposure at the site of action, target occupancy, and expression of functional pharmacological activity. The determination of PK/PD relationships across species can help understand how exposure drives response, which can be used to predict PK/PD in humans and determine optimal doses and regimens for maximal clinical benefit. Creative Biolabs has built several modeling approaches available to translate PK/PD of non-IgG therapeutic antibodies from animals to humans.
Features of Our Non-IgG Service
- Extensive experience
- Advanced biotechnologies
- Fully customizable experimental design to expand beyond standard procedure
- Competitive price with the best quality
Non-IgG antibodies are a library of bioactive molecules for discovering more therapeutic agents. Adhering to the concept of striving for human health, Creative Biolabs has made great achievements in the field of antibody development and won good reputations in service providing. Recently, we have successfully developed our own non-igg antibody platform to offer high-quality non-IgG antibody products and one-stop custom services for diverse therapeutic applications. If you are interested in our services, please do not hesitate to contact us for more details.
References
- Panawala, L. Difference between immunoglobulin and antibody. 2017. http://pediaa.com/difference-between-immunoglobulin-and-antibody/
KINDLY NOTE
!! For Research Use Only. Our products and services are NOT intended for diagnostic or therapeutic applications.