A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells.
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 x 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 x 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 x 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.
Hönemann
D
D
Department of Hematology, Oncology and Tumor-Immunology, Helios Clinics, Robert-Rössle Cancer Center, University Medical Center Charité, Berlin, Germany.
Kufer
P
P
Rimpler
M M
MM
Chatterjee
M
M
Friedl
S
S
Riecher
F
F
Bommert
K
K
Dörken
B
B
Bargou
R C
RC
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000918:Antibody Specificity; D018941:Antigens, CD19 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D007167:Immunotherapy; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D017252:CD3 Complex; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins