title: The novel CA IX inhibition antibody chKM4927 shows anti-tumor efficacy in vivo.
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.
authors: Nephrology Research Laboratories, Nephrology R&D Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Ayami
authors: A
authors: Yamaguchi
authors: Innovative Technology Laboratories, Research Functions Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Katsuaki
authors: K
authors: Usami
authors: Immunology and Allergy Research Laboratories, Immunology and Allergy R&D Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Munetake
authors: M
authors: Shimabe
authors: Research Core Function Laboratories, Research Functions Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Kazumasa
authors: K
authors: Hasegawa
authors: Research Core Function Laboratories, Research Functions Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Masao
authors: M
authors: Asada
authors: Oncology Research Laboratories, Oncology R&D Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Kazuhiro
authors: K
authors: Motoki
authors: Open Innovation Department, R&D Division, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
authors: Tomoyuki
authors: T
authors: Tahara
authors: Innovative Technology Laboratories, Research Functions Unit, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan kazuhiro.masuda@kyowa-kirin.co.jp.
authors: Kazuhiro
authors: K
authors: Masuda
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004791:Enzyme Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: CAIX; antibody; antibody-dependent cellular cytotoxicity; carbonic anhydrase; kidney cancer