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Structure-function relationships of the variable domains of monoclonal antibodies approved for cancer treatment.
- Source :
-
Critical reviews in oncology/hematology [Crit Rev Oncol Hematol] 2007 Dec; Vol. 64 (3), pp. 210-25. Date of Electronic Publication: 2007 Jul 12. - Publication Year :
- 2007
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal genetics
Antibodies, Monoclonal physiology
Binding Sites, Antibody
Humans
Immunoglobulin Variable Region genetics
Immunotherapy
Models, Biological
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Interaction Mapping
Protein Structure, Tertiary genetics
Protein Structure, Tertiary physiology
Recombinant Fusion Proteins therapeutic use
Sequence Homology, Amino Acid
Structure-Activity Relationship
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal therapeutic use
Immunoglobulin Variable Region chemistry
Immunoglobulin Variable Region physiology
Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1040-8428
- Volume :
- 64
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Critical reviews in oncology/hematology
- Publication Type :
- Academic Journal
- Accession number :
- 17624800
- Full Text :
- https://doi.org/10.1016/j.critrevonc.2007.04.011