Chimeric antibodies are antibodies that combine parental antibody variable regions and any acceptor constant area. Chimeric antibodies are hybrid molecules composed of different species' domains. For instance, the Fc region or all constant regions of a mouse monoclonal antibody (mAb) can be replaced with those of a human or another species' antibody.
The reason for doing this is due to the issues that arise when using mouse mAbs therapeutically. When administered to human patients, the foreign protein triggers an immune response, rendering chronic antibody treatment ineffective and causing complications due to immune complex formation. This is referred to as the human anti-mouse antibody (HAMA) response. By humanizing as much of the non-antigen-binding part of the antibody as possible, this response is reduced without affecting antigen binding. However, even with all constant regions replaced, there can still be enough of an anti-mouse response to cause problems.
The process can be taken further by replacing only the CDR regions and inserting them into a human framework, a technique known as CDR grafting. This is accomplished using polymerase chain reaction (PCR) techniques, site-directed mutagenesis, or synthetic oligonucleotides. CDR grafting takes advantage of the many well-characterized mouse mAbs already available that are otherwise unsuitable for therapy. Many of the therapeutic agents initially approved for therapy were constructs of this nature. It has been shown that merely transferring the loops themselves may not be enough to retain binding affinity since the human framework residues can affect the orientation of the loop and may require modification. However, it is also possible to retain antigen binding by only replacing the surface residues within the CDR region, a process called resurfacing.
There are two mainly applications of chimeric antibodies: Antibody chimerization is a preliminary step before antibody humanization in order to associate biological function to parental antibody and to decrease its immunogenicity. Alternatively, chimeric antibodies can be employed for therapeutic purposes in particular diseases or under certain conditions (variable domain with high GI). The second one is diagnostic use: Chimeric antibodies are the best alternative to serum, calibrators and positive controls in diagnostics assays. They are particularly suitable as they can be produced in unlimited quantities and homogeneous (preservation of antibody specificity and affinity.
Alpha Lifetech Inc. has developed a proprietary strategy for the rapid production of chimeric antibodies including full-length rat/human, mouse/human, mouse/rabbit, rat/rabbit and other hybrid antibodies. The company’s proprietary chimeric antibody technology allows you to specify your requirements for expression and characterization. The company has extensive experience in constructing and expressing recombinant or chimeric antibodies of various isotypes, including modified constant regions. We also specialize in expression in mammalian cells using recombinant mammalian expression systems.