Importance of Non-IgG Antibody Developability Improvement
Non-IgG antibodies have shown great potential in applications in diagnostics, immunotherapy, and so on. However, there are still many obstacles in front of the non-IgG antibodies' application. IgA for example, due to aggregate formation, there are issues in recombinant IgA production and subsequent purification processes. Besides, heterogeneity in oligosaccharide content of IgA because of multiple N-glycosylation motifs. And at last, the short serum half-life of IgA is also a technical limitation that withholds IgA from entering clinical studies. Thus in order to advance IgA antibodies as therapeutic agents, developability improvement is undoubtedly required.
Fig.1 Schematic overview of IgG and IgA formats. (van Tetering, 2020)
Examples of Non-IgG Antibody Developability Improvement
IgA has two subclasses, IgA1 and IgA2. IgA1 with an extended hinge region may offer higher avidity antigen binding with distantly spaced antigens, but it is more vulnerable to proteolysis by enzymes from pathogenic bacteria. IgA, especially the IgA2 isoform, has been shown to be superior to IgG1 in recruiting human polymorphonuclear (PMN) as effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC). In addition, antibody-dependent cellular phagocytosis (ADCP) by human peripheral blood neutrophils is more effectively mediated by IgA than by IgG. The IgA dimer format may be preferable in certain disease settings. However, the development of an IgA dimer is more challenging than that of a monomer. Toward that end, a recombinant dimeric IgA against epidermal growth factor receptor (EGFR) was produced and shown to mediate effective tumor cell killing. Importantly, the dimeric IgA, but not the monomeric IgA or IgG, was directionally transported by the polymeric Ig receptor through an epithelial cell monolayer in vitro. This has important implications for the IgA dimer as a potential anti-infectious agent at the mucosa.
Services at Creative Biolabs
Non-IgG antibody developability improvement has become a hot point in non-IgG research because of its potential to reveal more applications of non-IgG in more fields. Focusing on antibody researches over years, Creative Biolabs has also thrown our sights on non-IgG antibodies. With strong foundations, state-of-art technologies, and experienced experts, we are confident in providing our customers with satisfying non-IgG antibody developability improvement services.
If you are interested in our non-IgG antibody developability improvement services or you have any other questions, please don't hesitate to contact us for more information.
- van Tetering, G.; et al. Fc Engineering Strategies to Advance IgA Antibodies as Therapeutic Agents. Antibodies (Basel). 2020, 9(4).
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