Dissecting Immunogenicity of Monoclonal Antibodies
Abstract
The potential of monoclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb. A growing research effort to "humanize" mAb has focused primarily on the structure or sequence of the antibody variable (V) region domains. However, these approaches may ultimately suffer, as they overlook the requirement of T cell help for the immune counter-reaction and the potential of somatic hypermutation and V-D-J recombination to generate target T cell epitopes within mAb V regions. My approach focuses on this issue. In order to understand seine basic principals concerning anti-immunoglobulin immune responses, I have developed a panal of T cell hybridomas, new transgenic mice and a tetrameric staining reagent. Studies with these tools strongly support our basic hypothesis that T cells are tolerant of endogenous immunoglobulin-derived diversity. I have also obtained a panal of T cell hybridomas that are specific for the CDR3 region of a monoclonal antibody supporting our hypothesis that junctional diversity may provide a source of T cell epitopes within a monoclonal antibody. Finally, I have addressed the global nature of T cell responses to junctional diversity with an adoptove transfer system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417364
Entities
People
- Christopher M Snyder
- Lawrence J. Wysocki
Organizations
- National Jewish Health