The novel CA IX inhibition antibody chKM4927 shows anti-tumor efficacy in vivo

Anticancer Res. 2015 Apr;35(4):1997-2004.

Abstract

Carbonic anhydrase IX (CA IX) is an attractive target for cancer therapy. Many anti-CA IX antibodies have been reported but few have been shown to possess inhibition activity. Furthermore, effective use of CA IX-inhibition antibodies for cancer immunotherapy has not been well-validated since data are mainly limited to in vitro assays. In this study, we established that chKM4927, an anti-CA IX chimeric antibody, recognizes CA IX and has CA IX-specific inhibition activity. ChKM4927 also retains antibody-dependent cellular cytotoxicity (ADCC) activity against CA IX-expressing cancer cells. Compared to controls, chKM4927 treatment (10 mg/kg) showed anti-tumor activity in the VMRC-RCW xenograft model in vivo. ChKM4927-attenuated ADCC activity showed equally effective anti-tumor activity. These results suggest that the CA IX-inhibition antibody chKM4927 has an anti-tumor effect in the VMRC-RCW xenograft model via an ADCC-independent mechanism.

Keywords: CAIX; antibody; antibody-dependent cellular cytotoxicity; carbonic anhydrase; kidney cancer.

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / therapeutic use
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / immunology*
  • Carbonic Anhydrases / therapeutic use
  • Cell Line, Tumor
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / immunology
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Enzyme Inhibitors
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases