Fully human antibodies from transgenic mouse and phage display platforms.
Over the past two decades, technologies have emerged for generating monoclonal antibodies (MAbs) derived from human immunoglobulin gene sequences. These fully human MAbs provide an alternative to re-engineered, or de-immunized, rodent MAbs as a source of low immunogenicity therapeutic antibodies. There are now two marketed fully human therapeutic MAbs, adalimumab and panitumumab, and several dozen more in various stages of human clinical testing. Most of the drugs, including adalimumab and panitumumab, were generated using either phage display or transgenic mouse platforms. The reported clinical experience with fully human MAbs demonstrates that these two platforms are, and should continue to be, a significant source of active and well tolerated experimental therapeutics. While this body of reported clinical data does not yet provide a clear distinction between the platforms, the available descriptions of the drug discovery processes used to identify the clinical candidates highlight one difference. It appears that lead optimization is more commonly applied to phage display derived leads than transgenic mouse derived leads.
Lonberg
Nils
N
Medarex, Milpitas, CA 95035, United States. nlonberg@medarex.com
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D019151:Peptide Library; D015202:Protein Engineering; D053245:RANK Ligand / Q000276:immunology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015815:Cell Adhesion Molecules; C556707:Ctla4 protein, mouse; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D053759:Interleukin-23; D019151:Peptide Library; D053245:RANK Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C512478:EGFR protein, human; D066246:ErbB Receptors