In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment.

Abstract

In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorex(R)). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab.

• Authors: Stefanie Naundorf, Susanne Preithner, Petra Mayer, Sandra Lippold, Andreas Wolf, Frank Hanakam, Iduna Fichtner, Peter Kufer, Tobias Raum, Gert Riethmüller, Patrick A Baeuerle, Torsten Dreier
• Journal: International journal of cancer (Int J Cancer) Vol. 100 Issue 1 Pg. 101-10 (Jul 01 2002) ISSN: 0020-7136 [Print] United States
• PMID: 12115595 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal, Murine-Derived
• Antigens, Neoplasm
• Cell Adhesion Molecules
• Epithelial Cell Adhesion Molecule
• adecatumumab
• Edrecolomab
• Complement System Proteins

Topics

• Animals
• Antibodies, Monoclonal (immunology, metabolism, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antibodies, Monoclonal, Murine-Derived
• Antibody-Dependent Cell Cytotoxicity (immunology)
• Antigens, Neoplasm (immunology)
• CHO Cells
• Cell Adhesion Molecules (immunology, metabolism, therapeutic use)
• Colonic Neoplasms (pathology, therapy)
• Complement System Proteins (immunology)
• Cricetinae
• Cytotoxicity, Immunologic (immunology)
• Epithelial Cell Adhesion Molecule
• Humans
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms (therapy)
• Tumor Cells, Cultured