HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schoonbroodt, S. Articles by Hoet, R. M. Search for Related Content PubMed PubMed Citation Articles by Schoonbroodt, S. Articles by Hoet, R. M.

Engineering Antibody Heavy Chain CDR3 to Create a Phage Display Fab Library Rich in Antibodies That Bind Charged Carbohydrates

Sonia Schoonbroodt^*, Mieke Steukers^*, Malini Viswanathan, Nicolas Frans^*, Marie Timmermans^*, Anita Wehnert^*, Minh Nguyen^*, Robert Charles Ladner^1, and René M. Hoet^2,*

^* Dyax SA, Liege, Belgium; and Dyax Corp., Cambridge, MA 02139

A number of small charged carbohydrate moieties have been associated with inflammation and cancer. However, the development of therapeutic Abs targeting these moieties has been hampered by their low immunogenicity and their structural relationship to self-Ag. We report the design of an Ab repertoire enriched in Abs binding to small charged carbohydrates and the construction of a human Fab phagemid library, "FAB-CCHO." This library combines L chain Ig sequences from human donors and H chain synthetic diversity constructed in key Ag contact sites in CDRs 1, 2, and 3 of the human framework V_H3–23. The H chain CDR3 has been engineered to enrich the library in Abs that bind charged carbohydrates by the introduction of basic residues at specific amino acid locations. These residues were selected on the basis of anti-carbohydrate Ab sequence alignment. The success of this design is demonstrated by the isolation of phage Abs against charged carbohydrate therapeutic target Ags such as sulfated sialyl-Lewis X glycan and heparan sulfate.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Robert C. Ladner, Dyax Corp., 300 Technology Square, Cambridge, MA 02139-3515. E-mail address: bladne{at}dyax.com

² Current address: Genmab, The Netherlands (R.Hoet{at}genmab.com).

³ Abbreviations used in this paper: GAG, glycosaminoglycan; HS, heparan sulfate.

This article has been cited by other articles:

				A. H. Lucas and D. C. Reason Comment on "Engineering Antibody Heavy Chain CDR3 to Create a Phage Display Fab Library Rich in Antibodies That Bind Charged Carbohydrates" J. Immunol., May 1, 2009; 182(9): 5160 - 5161. [Full Text] [PDF]