In recent decades, monoclonal antibodies have become the most successful class of biotech drugs in the fields of hematology, oncology, autoimmune diseases, and infections. Besides the traditional IgG, IgA might be a great alternative since it recruits different effector cells. Based on years of experience, now Creative Biolabs provides professional IgA production and purification services for our universal customers.
Introduction of IgA Antibody
In humans, IgA presents the most abundant antibody class at mucosal surfaces and the second prevalent antibody in serum. Human serum contains mostly monomeric IgA and constitutes 15-20% of the whole immunoglobulins, while IgA exists in a dimeric and secretory form at mucosal surfaces. Similar to the IgG antibody, IgA monomer contains two heavy chains and two light chains (κ or λ), which together form the constant and variable regions of IgA. IgA antibody acts as the first line of humoral immune at mucosal surfaces with two subclasses IgA1 and IgA2. The ratio of IgA1: IgA2 is approximately 9:1 in human serum. IgA1 is the predominant isotype in plasma that contains a 13 amino acid hinge region that enables it to have a more extended reach.
Despite the fact that IgG is the classical isoform for all available cancer therapies, IgA presents great advantages as a therapeutic agent. Firstly, monomeric IgA is more effective than IgG for the recruit of polymorphonuclear neutrophils, which are the most abundant effector cell population in humans for antibody-dependent cellular cytotoxicity against tumor cells. Secondly, the dimeric IgA enhances its signaling capacity on tumor cells and allows transportation into mucosal secretions, resulting in the targeting improvement in certain tumors.
Fig.1 Different forms of IgA. (Reinhart, 2015)
IgA Production and Purification
Because of different subclasses, existing form, and glycosylation, traditional production and purification strategies for IgG antibodies are not quite suitable for IgA. The production of IgA antibodies using hybridoma technologies tend to immunize animals via the oral presentation of an antigen, because oral immunization can effectively stimulate mucosal immunity with increased frequency of IgA-producing B cells in the spleen.
How Did We Do at Creative Biolabs?
Transgenic mouse α1KI enables IgA monoclonal antibodies production by classical mice hybridoma technique. In addition, both monomeric IgA and dimeric isoform can be produced by recombinant technology based on our professional Expression System Platform. We have developed a comprehensive IgA expression system to meet any requirement of our clients, which extensively comprises Chinese hamster ovary (CHO) cells, myeloma cells, baby hamster kidney cells, etc. This system can offer a full range of cell lines which are widely used for preparing and optimizing the IgA antibodies to improve the clinical efficacy and repeatability of these antibodies in different diseases therapy. Once the sequence is provided, we can start with gene synthesis and plasmid construction. According to the subsequent transient transfection and stable cell line culture, IgA antibodies can be obtained. Please note that IgA antibodies are expressed as a dimer linked by a J-chain.
In order to obtain purified IgA for further basic research or clinical usage, the purification method is really important. Different from the normal antibodies, the optional IgA purification methods include lectin-chromatography, affinity chromatography (protein A/G/L and peptide M), exchange chromatography, and ligand peptide-chromatography. Among these, peptide M affinity chromatography performs better in IgA purification since that peptide M can bind to IgA antibodies with high affinity and specificity.
Fig.2 Expression in CHO cells of recombinant monomeric, dimeric, and secretory IgA. (Corthésy, 1999)
Creative Biolabs is your best choice in terms of IgA antibodies production and purification owing to decades of antibody development experience and all-around technology platforms. Our seasoned scientists can customize the most suitable products and services according to the specific requirements of customers.
Please feel free to contact us or send us an inquiry if you are interested in non-IgG therapeutic antibodies.
References
- Reinhart, D.; and Kunert, R. Upstream and downstream processing of recombinant IgA. Biotechnology Letters, 2015,12(7): 693-702.
- Corthésy, B.; Spertini, F. Secretory immunoglobulin A: from mucosal protection to vaccine development. Biological Chemistry. 1999, 380(11): 1251-1262.
KINDLY NOTE
!! For Research Use Only. Our products and services are NOT intended for diagnostic or therapeutic applications.