The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies Journal Article
| Authors: | Rader, C.; Ritter, G.; Nathan, S.; Elia, M.; Gout, I.; Jungbluth, A. A.; Cohen, L. S.; Welt, S.; Old, L. J.; Barbas, C. F. 3rd |
| Article Title: | The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies |
| Abstract: | The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic applications for decades, would be an attractive source for the generation of therapeutic human antibodies. The humanization of rabbit antibodies, however, has not been reported. Here we use phage display technology to select and humanize antibodies from rabbits that were immunized with human A33 antigen which is a target antigen for the immunotherapy of colon cancer. We first selected rabbit antibodies that bind to a cell surface epitope of human A33 antigen with an affinity in the 1 nM range. For rabbit antibody humanization, we then used a selection strategy that combines grafting of the complementarity determining regions with framework fine tuning. The resulting humanized antibodies were found to retain both high specificity and affinity for human A33 antigen. |
| Keywords: | nonhuman; antigen expression; animal cell; animals; gene library; enzyme linked immunosorbent assay; animalia; amino acid sequence; molecular sequence data; species specificity; immunotherapy; antigen specificity; membrane glycoproteins; immunogenicity; nucleotide sequence; base sequence; antibody specificity; dna flanking region; antibodies; phage display; antibody affinity; immunization; rabbits; rabbit; polyclonal antibody; dna library; oryctolagus cuniculus; humans; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 275 |
| Issue: | 18 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2000-05-05 |
| Start Page: | 13668 |
| End Page: | 13676 |
| Language: | English |
| DOI: | 10.1074/jbc.275.18.13668 |
| PUBMED: | 10788485 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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