title: Physical and biological properties of homophilic therapeutic antibodies.
abstract: Homophilic antibodies have been discovered in mice and primates and can also be engineered. Compared to conventional antibodies, homophilic antibodies form lattices on targets leading to enhanced binding via polyvalent attachment. Previously, we have observed a paradoxical dose/potency effect with an engineered homophilic antibody against a human lung cancer tumor. Here, we have investigated some biophysical properties of homophilic antibodies and also studied the inhibition of human tumor growth in a xenograft model using homophilic Herceptin. Dimerization and viscosity of two homophilic antibodies are greater at physiological temperature than at 4°C. Similarly, binding to solid-phase antigen is greater at 37°C than at room temperature or 4°C. Dimer formation is higher at therapeutic concentration, supporting the notion that preformed dimers in solution are the effective molecular species responsible for polyvalent target binding and enhanced therapeutic potency.
authors.affiliation: Department of Microbiology and Immunology, Markey Cancer Center, University of Kentucky, 124A Combs Building, 800 Rose St., Lexington, KY 40536, USA. Ajbrya0@uky.edu
authors.forename: Ann Jay
authors.initials: AJ
authors.lastname: Bryan
authors.forename: Heinz
authors.initials: H
authors.lastname: Kohler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D000068878:Trastuzumab; D014783:Viscosity; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab