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From rodent reagents to human therapeutics using antibody guided selection
Jane Osbourn1, Maria Groves, Tristan Vaughan
1Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge, CB1 6GH, UK. jane.osbourn@cambridgeantibody.com
Methods (San Diego, Calif.)
|April 26, 2005
Summary
Guided selection is a method for creating human antibodies from rodent antibodies. This process, using phage or ribosome display, has successfully generated therapeutic antibodies like HUMIRA for rheumatoid arthritis.
Area of Science:
- Biotechnology
- Immunology
- Protein Engineering
Background:
- Rodent antibodies are crucial for research and therapy but can elicit immune responses in humans.
- Developing humanized antibodies is essential to minimize immunogenicity and improve therapeutic efficacy.
Purpose of the Study:
- To describe the guided selection method for generating human antibodies from non-human sources.
- To highlight the versatility and success of guided selection in antibody engineering.
Main Methods:
- Guided selection involves a serial transition from rodent to human antibodies via rodent-human chimaerics.
- The process can utilize phage display or ribosome display technologies.
- Chimaeric antibodies can be generated in series or parallel, with options for retaining or modifying rodent CDR3 sequences.
Main Results:
- Guided selection has been successfully applied to generate human versions of rodent antibodies.
- This method has produced clinically relevant antibodies, such as HUMIRA (adalimumab).
- HUMIRA, an inhibitor of tumor necrosis factor-alpha, is approved for treating rheumatoid arthritis.
Conclusions:
- Guided selection is an effective strategy for producing human antibodies with desired characteristics.
- The method offers flexibility in antibody engineering and has led to successful therapeutic antibody development.
- This technique is vital for advancing antibody-based therapies and reducing potential adverse effects.