You have no items in your shopping cart.
Antibody Engineering
Chimeric Antibodies
Combining genetic fragments from different species to create highly specific therapeutic molecules with reduced immunogenicity.
A chimeric antibody is an antibody molecule composed of gene fragments from different species that have been combined through genetic engineering technology to create a novel molecule with highly particular properties.
These molecules were originally developed because of the severe lack of effectiveness of pure mouse antibodies in human therapeutics, as the foreign mouse protein consistently elicited a strong immune response (HAMA response). To effectively address this issue, chimeric antibodies were created—the specific variable regions of a mouse antibody were fused and linked directly to the constant regions of a human antibody. The precise combination of mouse and human regions allows the antibody to beautifully retain its original specificity while drastically reducing its immunogenicity.
.png)
1. Advantages of Chimeric Antibodies
By merging the targeting capabilities of murine antibodies with the immune compatibility of human antibodies, chimerics present several profound advantages over earlier therapeutic generations:
High Specificity
The variable regions of the parent mouse antibodies reliably retain their remarkably high specificity and binding affinity, ensuring they can accurately recognize and bind to the correct target antigens.
Low Immunogenicity
The integration of the constant region of human antibodies drastically reduces the human body's native immune response to the foreign therapeutic. This significantly improves both the long-term safety and overall clinical effectiveness of the antibodies.
Easy to Produce
Thanks to advanced genetic engineering, chimeric antibodies can be highly and efficiently produced at scale in standard expression systems such as Escherichia coli, yeast, or cultured mammalian cells.
2. Applications of Chimeric Antibodies
Chimeric antibodies have been successfully developed as highly targeted therapeutics for an extremely wide range of pathological conditions.
Abciximab, developed to successfully prevent severe platelet aggregation in the cardiovascular system, was the very first FDA-approved chimeric antibody therapeutic. Shortly after, Rituximab became the first chimeric cancer treatment, approved to treat non-Hodgkin’s lymphoma. Since then, many chimeric antibodies have been developed to treat a massive range of conditions, including Crohn’s disease, rheumatoid arthritis, general lymphomas, and multiple types of advanced cancer. These antibodies accurately target and bind to specific cellular antigens, exerting their therapeutic effects by activating the human immune system or directly inhibiting the activity of pathogens.
Emerging Fcα-Fcγ Chimeric Therapeutics
Of particular interest in modern cancer and HIV research is the construction of chimeric Fcα-Fcγ antibodies. Current standard therapeutics only involve IgG Fc regions; however, IgA offers profound immunological advantages of its own and has been proven to work synergistically alongside IgG. These novel chimeric antibodies have shown vastly improved effector functions while successfully possessing the longer half-life of IgG (over standard IgA), necessitating significant further research into this potential treatment option for HIV and aggressive cancer models.
3. References
- Chames, P., Van Regenmortel, M., Weiss, E. and Baty, D. (2009), Therapeutic antibodies: successes, limitations and hopes for the future. British Journal of Pharmacology, 157: 220-233. https://doi.org/10.1111/j.1476-5381.2009.00190.x
- Cottignies-Calamarte A, Tudor D, Bomsel M. Antibody Fc-chimerism and effector functions: When IgG takes advantage of IgA. Front Immunol. 2023 Feb 2;14:1037033. doi: 10.3389/fimmu.2023.1037033. PMID: 36817447; PMCID: PMC9933243.
- Eryl Liddell, Chapter 3.1 - Antibodies, Editor(s): David Wild, The Immunoassay Handbook (Fourth Edition), Elsevier, 2013, Pages 245-265, ISBN 9780080970370, https://doi.org/10.1016/B978-0-08-097037-0.00017-8.
- Lu, RM., Hwang, YC., Liu, IJ. et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27, 1 (2020). https://doi.org/10.1186/s12929-019-0592-z
- J. Med. Chem. 2020, 63, 5, 1908–1928. Publication Date: February 5, 2020. https://doi.org/10.1021/acs.jmedchem.9b01456
- Puregmaa Khongorzul, Cai Jia Ling, Farhan Ullah Khan, Awais Ullah Ihsan, Juan Zhang; Antibody–Drug Conjugates: A Comprehensive Review. Mol Cancer Res 1 January 2020; 18 (1): 3–19. https://doi.org/10.1158/1541-7786.MCR-19-0582