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Immunogenicity of engineered antibodies
William Ying Khee Hwang1, Jefferson Foote
1Singapore Health Services, Singapore General Hospital, Singapore.
Methods (San Diego, Calif.)
|April 26, 2005
Summary
Therapeutic antibodies can trigger anti-antibody responses (AAR). Engineering antibodies by replacing mouse components with human ones significantly reduces immunogenicity, with humanizing variable domains further decreasing AAR.
Area of Science:
- Immunology
- Biotechnology
- Pharmacology
Background:
- Therapeutic antibodies can elicit an anti-antibody response (AAR).
- Minimizing non-human structures in engineered antibodies is crucial for reducing immunogenicity.
- Understanding AAR to different antibody types informs therapeutic development.
Purpose of the Study:
- To review reported anti-antibody responses to various engineered antibodies.
- To assess the impact of different engineering strategies on antibody immunogenicity.
- To provide insights into reducing immune reactions to therapeutic antibodies.
Main Methods:
- Literature review of reported anti-antibody responses.
- Analysis of immunogenicity data for murine, chimeric, and humanized antibodies.
- Comparison of immunogenicity reduction achieved by different engineering approaches.
Main Results:
- Replacement of mouse immunoglobulin constant regions with human ones significantly reduces immunogenicity.
- Humanization of variable domains further decreases the anti-antibody response.
- Murine antibodies generally elicit higher AAR compared to chimeric and humanized forms.
Conclusions:
- Engineering strategies, particularly the use of human components, are effective in minimizing anti-antibody responses.
- Humanization of both constant and variable regions is key to developing less immunogenic therapeutic antibodies.
- Further research into antibody engineering can lead to safer and more effective antibody therapies.