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Tumor‐targeting and anti‐tumor activity of anti‐claudin‐3/‐4 antibody (1062.7)
Author(s) -
Kimura Yuka,
Li Xiangru,
Iida Manami,
Tada Minoru,
Ishii Akiko,
Watari Akihiro,
Fukasawa Masayoshi,
Yagi Kiyohito,
Kondoh Masuo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1062.7
Subject(s) - claudin , antibody , cancer research , hek 293 cells , biology , microbiology and biotechnology , receptor , tight junction , immunology , biochemistry
Claudins (CLDNs) comprise a tetra‐transmembrane protein family with ~20 members, which are located in the lateral membrane between adjacent epithelial cells. Because of loss of cellular polarity during malignant transformation, CLDN often migrates from the lateral membrane and becomes exposed on epithelial cell surfaces. CLDN3 and CLDN4 are targets for tumor therapy because they are overexpressed in various malignant tumors. We previously optimized a protocol for immunization with CLDN and developed 8 rat anti‐CLDN4 monoclonal antibodies, one of which recognized both CLDN3 and CLDN4. In this study, we focused on the CLDN3/4 antibody. The CLDN3/4 antibody showed high affinity for CLDN4 (K D value: 4.3 nM). We fluorescently labeled the CLDN3/4 antibody and intravenously injected it into mice bearing tumors (human colon cancer Lovo cells, or human gastric cancer MKN74 cells). The CLDN3/4 antibody accumulated in tumor tissues and attenuated tumor growth without apparent adverse effects in the Lovo‐ and MKN74‐bearing mice. Furthermore, CLDN3/4 antibody activated the Fcγ receptor in vitro . Therefore, the CLDN3/4 antibody may exert its anti‐tumor activity through antibody‐dependent cellular toxicity. These findings suggest that the CLDN3/4 antibody is a candidate anti‐tumor agent. Grant Funding Source : supported by the Ministry of Health, Labor, and Welfare of Japan