Tumor-targeting and anti-tumor activity of anti-claudin-3/-4 antibody (1062.7)

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 (KD 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-b...