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

  • Naundorf S
  • Preithner S
  • Mayer P
 et al. 
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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.

Author-supplied keywords

  • Animals
  • Antibodies, Monoclonal/*immunology/metabolism/*the
  • Antibody-Dependent Cell Cytotoxicity/immunology
  • Antigens, Neoplasm/*immunology
  • CHO Cells
  • Cell Adhesion Molecules/*immunology/metabolism/*th
  • Colonic Neoplasms/pathology/therapy
  • Complement System Proteins/immunology
  • Cricetinae
  • Cytotoxicity, Immunologic/immunology
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms/*therapy
  • Tumor Cells, Cultured

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Authors

  • S Naundorf

  • S Preithner

  • P Mayer

  • S Lippold

  • A Wolf

  • F Hanakam

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