The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies

Christoph Rader, Gerd Ritter, Sheila Nathan, Marikka Elia, Ivan Gout, Achim A. Jungbluth, Leonard S. Cohen, Sydney Welt, Lloyd J. Old, Carlos F. Barbas

Research output: Contribution to journalArticle

95 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13668-13676
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number18
DOIs
Publication statusPublished - 5 May 2000

Fingerprint

Rabbits
Antibodies
Antibodies, Monoclonal, Humanized
Therapeutics
Complementarity Determining Regions
Bacteriophages
Immunotherapy
Colonic Neoplasms
Epitopes
Tuning
Display devices
Technology
Antigens
human GPA33 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies. / Rader, Christoph; Ritter, Gerd; Nathan, Sheila; Elia, Marikka; Gout, Ivan; Jungbluth, Achim A.; Cohen, Leonard S.; Welt, Sydney; Old, Lloyd J.; Barbas, Carlos F.

In: Journal of Biological Chemistry, Vol. 275, No. 18, 05.05.2000, p. 13668-13676.

Research output: Contribution to journalArticle

Rader, C, Ritter, G, Nathan, S, Elia, M, Gout, I, Jungbluth, AA, Cohen, LS, Welt, S, Old, LJ & Barbas, CF 2000, 'The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies', Journal of Biological Chemistry, vol. 275, no. 18, pp. 13668-13676. https://doi.org/10.1074/jbc.275.18.13668
Rader, Christoph ; Ritter, Gerd ; Nathan, Sheila ; Elia, Marikka ; Gout, Ivan ; Jungbluth, Achim A. ; Cohen, Leonard S. ; Welt, Sydney ; Old, Lloyd J. ; Barbas, Carlos F. / The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 18. pp. 13668-13676.
@article{67c3a1eb1f5e4d02857dc995375276ec,
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.",
author = "Christoph Rader and Gerd Ritter and Sheila Nathan and Marikka Elia and Ivan Gout and Jungbluth, {Achim A.} and Cohen, {Leonard S.} and Sydney Welt and Old, {Lloyd J.} and Barbas, {Carlos F.}",
year = "2000",
month = "5",
day = "5",
doi = "10.1074/jbc.275.18.13668",
language = "English",
volume = "275",
pages = "13668--13676",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - The rabbit antibody repertoire as a novel source for the generation of therapeutic human antibodies

AU - Rader, Christoph

AU - Ritter, Gerd

AU - Nathan, Sheila

AU - Elia, Marikka

AU - Gout, Ivan

AU - Jungbluth, Achim A.

AU - Cohen, Leonard S.

AU - Welt, Sydney

AU - Old, Lloyd J.

AU - Barbas, Carlos F.

PY - 2000/5/5

Y1 - 2000/5/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034607856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034607856&partnerID=8YFLogxK

U2 - 10.1074/jbc.275.18.13668

DO - 10.1074/jbc.275.18.13668

M3 - Article

C2 - 10788485

AN - SCOPUS:0034607856

VL - 275

SP - 13668

EP - 13676

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -