title: Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells.
abstract: Monoclonal antibodies (mAbs) that exert antitumor activity can do so by virtue of their effector function and/or their ability to signal growth arrest or cell death. In this study, we demonstrate that mAbs which have little or no signaling activity-i.e., anti-CD19, CD20, CD21, CD22 and Her-2-can become potent antitumor agents when they are converted into IgG-IgG homodimers. The homodimers exert antigrowth activity by signaling G0/G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and, in the case of the anti-CD19 mAb, did not require an Fc portion. These results offer the possibility that homodimers of other tumor-reactive mAbs which have little antitumor activity as monomers might be potent, antitumor agents.
authors.affiliation: Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghetie
authors.forename: E M
authors.initials: EM
authors.lastname: Podar
authors.forename: A
authors.initials: A
authors.lastname: Ilgen
authors.forename: B E
authors.initials: BE
authors.lastname: Gordon
authors.forename: J W
authors.initials: JW
authors.lastname: Uhr
authors.forename: E S
authors.initials: ES
authors.lastname: Vitetta
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D019281:Dimerization; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007074:Immunoglobulin G