Toward the production of bispecific antibody fragments for clinical applications.
The clinical potential of bispecific antibodies (BsAb) has been hindered by the difficulty of obtaining clinical grade material, together with the immunogenicity of rodent-derived BsAb in patients. The supply issue is being directly addressed by recombinant methods for BsAb fragment production reviewed here. The immunogenicity issue will likely be overcome by the use of humanized or human antibodies. Currently, three technologies appear suitable for the production of BsAb fragments for clinical applications: BsF(ab')2 assembled from Fab' fragments expressed in Escherichia coli, BsF(ab')2 assembled using leucine zippers, and diabodies.
Carter
P
P
Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
Ridgway
J
J
Zhu
Z
Z
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use; D000918:Antibody Specificity; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D016350:Leucine Zippers; D046911:Macromolecular Substances; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000302:isolation & purification* / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D003432:Cross-Linking Reagents; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D046911:Macromolecular Substances; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins