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

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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., Kufer, P., Rimpler, M.M., Chatterjee, M., Friedl, S., Riecher, F., Bommert, K., 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
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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