title: [Directed molecular evolution of antibodies].
abstract: Antibodies play a key role in the immune system, are characterized by a homogeneous overall structure and by their ability to interact with an almost unlimited number of compounds. Encoded by a fixed number of genes, they acquire their specificity and affinity of recognition after a succession of genetic recombination and molecular mutation processes. Since the pioneer works of Kohler and Milstein in 1975 describing the possibility of producing monoclonal antibodies with pre-determined specificity, the use of antibodies in the fields of research, diagnosis and therapy has never stopped increasing. Thus, about twenty monoclonal antibodies have yet been authorized to be used in human immunotherapy. However, a majority of these molecules have been engineered to bring them into line with their clinical use: chimerization, humanization, recombinant expression of single or fused fragments. Furthermore, the recent development of in vitro molecular evolution approaches now make it possible to engineer the affinity, the specificity as well as the stability of monoclonal antibodies. The potential of in vitro molecular evolution of antibodies will be illustrated through the example of the specificity improvement of an anti-progesterone antibody.
authors.affiliation: UMR CEA/bioMérieux, CEA, DSV, DIEP, Gif Sur Yvette, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dubreuil
authors.forename: Bruno
authors.initials: B
authors.lastname: Muller
authors.forename: Marc
authors.initials: M
authors.lastname: Bossus
authors.forename: Alexandra
authors.initials: A
authors.lastname: Savatier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ducancel
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry* / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics; D000918:Antibody Specificity; D046528:Chimerism; D019020:Directed Molecular Evolution / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D010446:Peptide Fragments