The Fc portion of UV3, an anti-CD54 monoclonal antibody, is critical for its antitumor activity in SCID mice with human multiple myeloma or lymphoma cell lines

Abstract

UV3 is a monoclonal antibody that recognizes human CD54 (intercellular adhesion molecule-1), and it was generated for the therapy of human multiple myeloma. In a severe combined immunodeficient (SCID) xenograft model of human multiple myeloma, UV3 significantly prolonged the survival of mice with either early or advanced stages of disease. However, the mechanism by which UV3 exerted its antitumor effect remained unknown. As reported previously UV3 could mediate antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity in vitro. F(ab)'2 fragments of UV3 had therapeutic efficacy in vivo, suggesting that effector functions were not critical. The purpose of this study was to further define the importance of the Fc portion of UV3 for its antitumor activity in vivo. To this end, we examined the effect of an "ultrapure" preparation of UV3 F(ab)'2 to treat SCID mice xenografted with either ARH-77 cells, a human multiple myeloma cell line, or Daudi cells, a human Burkitt's lymphoma cell line. In addition, we evaluated different doses of UV3 immunoglobulin G (IgG) in these mice to determine the minimum amount of IgG that would produce a therapeutic effect. Data obtained from this study suggest that (1) the Fc portion of UV3 is critical for its antitumor activity in vivo, (2) low levels of UV3 IgG in a preparation of F(ab)'2 fragments account for all of its in vivo activity in multiple myeloma and most of its activity in lymphoma, and (3) UV3 IgG significantly prolongs the survival of SCID/ARH-77 mice as well as SCID/Daudi mice.