Structure–function relationships of the variable domains of monoclonal antibodies approved for cancer treatment

Magdelaine-Beuzelin, Charlotte, Kaas, Quentin, Wehbi, Vanessa, Ohresser, Marc, Jefferis, Roy, Lefranc, Marie-Paule and Watier. Hervé (2007) Structure–function relationships of the variable domains of monoclonal antibodies approved for cancer treatment. Critical reviews in Oncology/Hematology, 64 3: 210-225. doi:10.1016/j.critrevonc.2007.04.011


Author Magdelaine-Beuzelin, Charlotte
Kaas, Quentin
Wehbi, Vanessa
Ohresser, Marc
Jefferis, Roy
Lefranc, Marie-Paule
Watier. Hervé
Title Structure–function relationships of the variable domains of monoclonal antibodies approved for cancer treatment
Journal name Critical reviews in Oncology/Hematology   Check publisher's open access policy
ISSN 1040-8428
1879-0461
Publication date 2007-12
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.critrevonc.2007.04.011
Volume 64
Issue 3
Start page 210
End page 225
Total pages 16
Place of publication Shannon, Co. Clare Ireland
Publisher Elsevier
Language eng
Subject 060102 Bioinformatics
Abstract Due to their exquisite specificity for a given epitope on the target antigen, recombinant monoclonal antibodies (rmAb) can deliver “targeted therapy” in oncology. This review focuses on the structural bases of “antigen specificity” to aid clinical researchers and pharmacologists in managing these new drugs. The fine structure of the Fv (Fragment variable) module (combination of VH and VL domains) from the five unconjugated antibodies currently approved for cancer treatment, namely rituximab, cetuximab, alemtuzumab, trastuzumab and bevacizumab, is presented and analysed. Co-crystal and functional studies are reviewed to define rmAb residues contributing to antigen binding site (paratope)–epitope interfaces. The genetic origin of these recombinant monoclonal antibodies, determined through the IMGT/3Dstructure-DB database and IMGT/V-QUEST (http://imgt.cines.fr), is presented, allowing the evaluation of homologies between antibodies and their closest germline human counterparts and hence their possible immunogenicity. Overall, the IMGT standards appear as a first and crucial step in the evaluation of recombinant antibodies.
Keyword Therapeutic antibodies
Variable domain
Paratope
Epitope
Oncology
Cancer
Rituximab
Cetuximab
Alemtuzumab
Trastuzumab
Bevacizumab
Monoclonal antibody
IMGT
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 21 Jan 2009, 11:12:31 EST by Judy Dingwall on behalf of Institute for Molecular Bioscience