Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells.
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.
Ghetie
M A
MA
Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Podar
E M
EM
Ilgen
A
A
Gordon
B E
BE
Uhr
J W
JW
Vitetta
E S
ES
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
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D007074:Immunoglobulin G