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T-cell-mediated lysis of B cells induced by a CD19xCD3 bispecific single-chain antibody is perforin dependent and death receptor independent

Item Type:Article
Title:T-cell-mediated lysis of B cells induced by a CD19xCD3 bispecific single-chain antibody is perforin dependent and death receptor independent
Creators Name:Gruen, M. and Bommert, K. and Bargou, R.C.
Abstract:A recently developed bispecific antibody construct, directed against CD19 and CD3 (bscCD19xCD3), induces T-cell-mediated lysis of allogeneic and autologous B cells in a specific and highly efficient manner. Since knowledge of the molecular mechanisms underlying this lysis is limited, a study on bscCD19xCD3-activated T-cell-effector pathways was performed. BscCD19xCD3-induced lysis of target B-cell lines Nalm-6, Daudi, and Raji and of autologous primary B cells is caused by the perforin-dependent granule-exocytosis pathway but not by the death ligands FasL, TRAIL, or TNF-α. When activated by bscCD19xCD3 and Raji cells, T cells express FasL mRNA, but incubation of Raji cells with cell-free supernatants from cytotoxicity experiments caused an upregulation of c-Flip 1, possibly accounting for the cells' insensitivity toward death-receptor-mediated lysis. In addition to granule exocytosis, Raji cells are lysed by at least one mechanism independent of perforin, which requires transport through the T cell's Golgi apparatus.
Keywords:B-NHL, Bispecific Antibody, Immunotherapy, Perforin, T cell
Source:Cancer Immunology Immunotherapy
ISSN:0340-7004
Publisher:Springer (Germany)
Volume:53
Number:7
Page Range:625-632
Date:1 January 2004
Official Publication:https://doi.org/10.1007/s00262-003-0496-2
PubMed:View item in PubMed

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