In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment.
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.
Naundorf
Stefanie
S
Micromet AG, Martinsried, Germany.
Preithner
Susanne
S
Mayer
Petra
P
Lippold
Sandra
S
Wolf
Andreas
A
Hanakam
Frank
F
Fichtner
Iduna
I
Kufer
Peter
P
Raum
Tobias
T
Riethmüller
Gert
G
Baeuerle
Patrick A
PA
Dreier
Torsten
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy; D003165:Complement System Proteins / Q000276:immunology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C460839:adecatumumab; C400149:Edrecolomab; D003165:Complement System Proteins