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Updated: Jul 9, 2026
09:42
Generation of Murine Monoclonal Antibodies by Hybridoma Technology
Published on: January 2, 2017
Human monoclonal antibodies from transgenic mice
1Medarex, 521 Cottonwood Drive, Milpitas, CA 95035, USA. nlonberg@medarex.com
Handbook of Experimental Pharmacology
|December 12, 2007
Summary
Therapeutic monoclonal antibodies (MAbs) have advanced significantly since 1986. Engineering these antibodies, particularly using transgenic mice to produce human versions, has overcome immunogenicity challenges, establishing a validated drug discovery platform.
Area of Science:
- Biotechnology
- Immunology
- Pharmacology
Background:
- Monoclonal antibodies (MAbs) are crucial therapeutics for various diseases, including cancer and autoimmune disorders.
- Early MAbs, often rodent-derived, faced immunogenicity issues, hindering widespread therapeutic acceptance.
- Technological advancements have focused on reducing MAb immunogenicity for improved clinical outcomes.
Purpose of the Study:
- To review the evolution of therapeutic monoclonal antibody (MAb) development.
- To highlight the impact of antibody engineering technologies in overcoming immunogenicity.
- To discuss the emergence and validation of transgenic mouse platforms for human MAb discovery.
Main Methods:
- Review of historical regulatory approvals and technological advancements in MAb engineering.
- Analysis of strategies to reduce MAb immunogenicity, including in vitro optimization.
- Examination of transgenic mouse technology for generating human antibody repertoires.
Main Results:
- Muromonomab-CD3 (1986) marked an early milestone in MAb therapy.
- Various engineering techniques have successfully reduced MAb immunogenicity.
- Panitumumab (2006), a fully human MAb from transgenic mice, validated this platform.
- Dozens of human MAbs from transgenic mice are now in clinical development.
Conclusions:
- Therapeutic MAb development has overcome significant hurdles, notably immunogenicity.
- Transgenic mouse technology represents a commercially validated and established platform for human MAb discovery.
- The success of human MAbs from transgenic mice signifies a new era in antibody-based therapeutics.
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