Engineering of monoclonal antibodies and antibody-based fusion proteins: successes and challenges.
Monoclonal antibodies (mAbs) and antibody-based fusion molecules have now come of age as therapeutics. Eighteen mAbs and two fusion molecules are on the market. mAbs directed against new targets are progressing at a rapid rate with the help of proteomics and genomics approaches. Many technical efforts have been made to generate a second-generation mAb with decreased immunogenicity and with optimised effector functions. The development of molecular engineering techniques applied to antibody molecules has also made it possible to design fusion molecules exhibiting different modules with bifunctional activities. Different approaches developed over the last two decades to generate and optimise therapeutic antibodies and antibody-based fusion molecules are described, with a particular focus on antibodies and fusion proteins used in oncology and inflammatory diseases. Some current technical challenges and trends are also discussed.
Teillaud
Jean-Luc
JL
University Paris 6-Pierre & Marie Curie, Unité INSERM 255, Centre de Recherches Biomédicales des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France. jean-luc.teillaud@u255.bhdc.jussieu.fr
D000818:Animals; D018033:Antibodies, Bispecific / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D020650:Combinatorial Chemistry Techniques; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D019151:Peptide Library; D015202:Protein Engineering; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D019151:Peptide Library; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins