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The immunogenicity of chimeric antibodies
M Brüggemann1, G Winter, H Waldmann
1Department of Pathology, Addenbrooke's Hospital, Cambridge, United Kingdom.
The Journal of Experimental Medicine
|December 1, 1989
Summary
Foreign antibody frameworks, particularly variable heavy (VH) regions, can trigger significant anti-antibody immune responses in mice. Even partially humanized (chimeric) antibodies elicit strong reactions, highlighting the immunogenicity of VH regions.
Area of Science:
- Immunology
- Antibody Engineering
- Xenotransplantation
Background:
- Antibodies are crucial therapeutic proteins, but their immunogenicity can limit efficacy.
- Understanding the immune response to antibodies, especially engineered ones, is vital for developing safer treatments.
Purpose of the Study:
- To investigate the immunogenicity of different antibody constructs in mice.
- To determine the contribution of variable heavy (VH) frameworks and constant heavy (CH) domains to anti-antibody responses.
Main Methods:
- Mice were immunized with model xenogeneic, chimeric, or self antibodies.
- Anti-antibody responses targeting different antibody regions (VH, CH) were analyzed.
Main Results:
- Self antibodies did not elicit a response.
- Highly xenogeneic antibodies induced strong responses, primarily against CH domains.
- Chimeric antibodies, with human VH frameworks, also elicited significant anti-VH responses.
- The anti-VH response magnitude was comparable to allotypic responses.
Conclusions:
- Foreign VH frameworks are immunogenic and can elicit substantial anti-antibody responses.
- Chimerization may not fully abrogate immunogenicity.
- Both V region immunogenicity and allotypic polymorphism are critical factors in anti-antibody responses.