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A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells

Item Type:Article
Title:A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells
Creators Name:Hoenemann, D. and Kufer, P. and Rimpler, M.M. and Chatterjee, M. and Friedl, S. and Riecher, F. and Bommert, K. and Doerken, B. and Bargou, R.C.
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.
Keywords:Bsp Wu-1 × CD3, Immunotherapy, Multiple Myeloma, Singlechain Bispecific Antibody, Wue-1
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group (U.K.)
Volume:18
Number:3
Page Range:636-644
Date:1 January 2004
Official Publication:https://doi.org/10.1038/sj.leu.2403264
PubMed:View item in PubMed

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