1. ¹Department of Hematology, Oncology and Tumor-Immunology, Helios Clinics, Robert-Rössle Cancer Center, University Medical Center Charité, Berlin, Germany
2. ²Institute of Immunology, University of Munich, Munich, Germany
3. ³Max-Delbrück Center for Molecular Medicine, Berlin, Germany

Correspondence: RC Bargou, Department of Hematology, Oncology and Tumor-Immunology, Helios Clinics, Robert-Rössle Cancer Center, University Medical Center Charité, Lindenberger Weg 80, 13125 Berlin, Germany. Fax: +49 30 9417 1398

⁴The first four authors contributed equally to this work

Received 10 September 2003; Accepted 17 November 2003; Published online 22 January 2004.

Abstract

The development of antibody-based strategies for the treatment of multiple myeloma (MM) has been hampered so far by the fact that suitable plasma cell-specific surface antigens have been missing. However, recently a novel monoclonal antibody, designated Wue-1, has been generated that specifically recognizes normal and malignant human plasma cells. Therefore, Wue-1 is an interesting and promising candidate to develop novel immunotherapeutic strategies for the treatment of MM. One variant for an antibody-based strategy is the bispecific antibody approach. Recombinant bispecific single-chain (bsc) antibodies are especially interesting candidates because they show exceptional biological properties. We have generated a novel MM-directed recombinant bsc antibody, bscWue-1 CD3, and analyzed the biological properties of this antibody using the MM cell line NCI-H929 and primary cells from the bone marrow of patients with MM. We were able to show that bscWue-1 CD3 induces efficient and selective T-cell-mediated cell death of NCI-H929 cells and primary myeloma cells in nine out of 11 cases. The bscWue-1 CD3 Ab is efficacious even at low E:T ratios, and with or without additional T-cell pre- or costimulation. Target cell lyses were specific for Wue-1 antigen-positive cells and could be blocked by the Wue-1 monoclonal antibody.