A Defucosylated Mouse Anti-CD10 Monoclonal Antibody (31-mG2a-f) Exerts Antitumor Activity in a Mouse Xenograft Model of Renal Cell Cancers.

CD10 is a cell surface metalloendopeptidase that cleaves and degrades many secreted physiologically active peptides by its enzymatic activity. Although CD10 expression has been found in various types of cells, its expression is increased in several cancers, including renal cancer. In this study, the antitumor activity of a novel anti-human CD10 monoclonal antibody (mAb) was investigated. A defucosylated mouse IgG_2a version of C₁₀Mab-31 (31-mG_2a-f) was created from an anti-CD10 mAb, C₁₀Mab-31 (IgG₁, kappa). Both C₁₀Mab-31 and 31-mG_2a-f specifically reacted with endogenous CD10 in renal cancer cells, VMRC-RCW, with the dissociation constant (K_D) values of 6.3 × 10^-9 M and 1.1 × 10^-9 M, respectively, indicating high binding affinity. To further examine the anti-CD10 mAb-mediated effector functions, the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were examined. The 31-mG_2a-f significantly exhibited ADCC and CDC against VMRC-RCW cells in vitro. Furthermore, 31-mG_2a-f exhibited antitumor activities in mouse xenografts of VMRC-RCW cells. These results suggest that 31-mG_2a-f exerts antitumor activities against CD10-expressing renal cancers and could be a valuable therapeutic candidate for treating them.