title: Construction and production of an IgG-like tetravalent bispecific antibody for enhanced therapeutic efficacy.
abstract: In past years, both laboratory and early clinical studies have demonstrated that biospecific antibodies (BsAbs) may have significant potential application in cancer therapy either by targeting tumor cells with cytotoxic agents including effector cells, radionuclides, drugs, and toxins, or by simultaneously blocking two relevant tumor targets, that is, growth factor receptors, thus neutralizing multiple receptor activation and downstream signal transduction pathways. A major obstacle in the development of BsAb has been the difficulty of producing the materials in sufficient quality and quantity by traditional technologies such as the hybrid hybridoma and chemical conjugation methods. The development of IgG-like BsAbs as therapeutic agents will depend heavily on the advances made in the design of recombinant BsAb constructs (or formats) and production efficiency. Here we describe a recombinant method for the construction and production of a novel IgG-like BsAb molecule, using the variable domains of two fully human antibodies as the building blocks.
authors.affiliation: ImClone Systems Inc., New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000096:biosynthesis* / Q000627:therapeutic use*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000627:therapeutic use*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008967:Molecular Biology / Q000379:methods*; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D018033:Antibodies, Bispecific; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors; D011972:Receptor, Insulin