It is well known that there are five main classes of Ig referred to as IgG, IgA, IgD, IgE, and IgM, divided according to the various genes encoding the constant regions of the heavy chain. While IgM is the largest antibody which is a pentamer consisting of five monomers, the very large molecule of IgM brings difficulty to work with in terms of reagent availability, purification, and specificity. On the contrary, more than 20 recombinant IgG antibody-based therapeutic drugs are now licensed for the treatment of a variety of diseases. Therefore, a vector with the IgG is a convenient approach to promote the transformation of specific IgM to a therapeutic antibody with clinic application potential by the expression of the chimeric antibody. As a world-leading biotech company, Creative Biolabs has been devoted to the development and application of antibodies. Over the past decades, we have launched established platforms and accumulated rich experience in the field of antibody engineering including IgM/IgG chimeric antibody research. Hence, it is our pleasure to share our idea of IgM/IgG chimeric antibody with our partners all over the world.
Introduction of IgM/IgG Chimeric Antibody
Chimerization or humanization of antibodies is a necessary process to reduce their immunogenicity when preparing mAbs for therapeutic purposes. Chimeric Antibodies are prepared by joining the Ig variable regions of a selected mouse hybridoma to human Ig constant regions while IgG is most generally. However, IgM antibodies appear early in the course of an infection and play an important role in the immune response. Due to the challenges in purification and storage caused by large molecular weight, IgM /IgG chimeric antibodies provide a pathway to develop novel therapeutic antibodies. Therefore, when an antibody is IgM type and RNA from its hybridoma is available, it is often desirable to convert it into an IgG format by cloning its cDNA to explore its full potential for many purposes.
Application of IgM/IgG Chimeric Antibody
The development of screening methods based on the display of large libraries of antibody fragments has allowed considerable advances for the in vitro isolation of mAbs, which established the foundation of engineered chimeric antibodies. Recently, some scientists have expressed chimeric IgM/IgG antibodies containing chicken antigen-binding regions of IgM and human constant regions of the IgG isoform. In this research, targeting vectors were produced by the knock-in of the human IgHG1 constant region at the chicken IgHM locus. Final genomic structure after integration of the knock-in plasmid and expected mRNA variants produced by alternative splicing. Finally, antigen-specific IgM/IgG chimeric antibodies can therefore be isolated directly by magnetic beads.
Fig.1 Cloning of IgM cDNA and construction of various IgM/IgG chimeric molecules. (Teye, 2017)
The development of engineered IgM/IgG chimeric antibody allows easier purification and wider application than IgM, which attracts more attention from many advanced groups including Creative Biolabs. If you are interested in the research of engineered IgM/IgG chimeric antibody, or for more details in the research of the therapeutic molecular field, please feel free to contact us.
Reference
- Teye, K.; et al. Multimerization is required for antigen binding activity of an engineered IgM/IgG chimeric antibody recognizing a skin-related antigen. Scientific Reports. 2017, 7(1): 8212.
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