Method for Reducing the Immunogenicity of Antibody Variable Domains
Description of Invention:
The current invention addresses a limitation of monoclonal antibodies used in immunotherapy. Monoclonal antibodies with high selectivity for human antigens are commonly produced in mice. However, when introduced into humans for therapy, the antibodies can be neutralized by the human immune system and their duration and effectiveness limited. Modification of non-human antibodies to avoid the human immune system often produces antibodies with reduced affinity for the antigen and which remain antigenic in humans.
The current invention provides a method for producing “humanized” antibodies that retain antigen binding properties but which have eliminated or reduced antigenicity. The method comprises substituting residues in the variable region of the non-human antibody with residues found in the variable region of human antibodies, with particular emphasis on residues that are solvent exposed and that are not adjacent to complementarity determining regions.
When tested in monkeys, the serum longevity of the “veneered” antibodies produced by the current invention was significantly greater than that of mouse antibodies or chimeric mouse-human antibodies. Accordingly, the technology could enhance the effectiveness of monoclonal antibodies designed for therapy of cancer or other diseases.
Cancer -Therapeutics-Immunoconjugates Cancer -Therapeutics
For Additional Information Please Contact: John Stansberry Ph.D.
NIH Office of Technology Transfer
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-5236
Email: stansbej@mail.nih.gov
Fax: (301) 402-0220
