Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct

Tools

Item Type:	Article
Title:	Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct
Creators Name:	Loeffler, A., Gruen, M., Wuchter, C., Schriever, F., Kufer, P., Dreier, T., Hanakam, F., Baeuerle, P.A., Bommert, K., Karawajew, L., Doerken, B. and Bargou, R.C.
Abstract:	Recently, we have shown that a novel recombinant bispecific single-chain antibody construct (bscCD19 x CD3), induces highly efficacious lymphoma-directed cytotoxicity mediated by unstimulated peripheral T lymphocytes. Functional analysis of bscCD19 x CD3 has so far been exclusively performed with human B lymphoma cell lines and T cells from healthy donors. Here we analysed the properties of bscCD19 x CD3 using primary B cells and autologous T cells from healthy volunteers or patients with B-cell chronic lymphocytic leukaemia (B-CLL). We show that bscCD19 x CD3 induces T-cell-mediated depletion of nonmalignant B cells in all four cases and depletion of primary lymphoma cells in 22 out of 25 cases. This effect could be observed at low effector-to-target (E:T) ratios and in the majority of cases without additional activation of autologous T cells by IL-2. Even in samples derived from patients heavily pretreated with different chemotherapy regimens, strong cytotoxic effects of bscCD19 x CD3 could be observed. The addition of bscCD19 x CD3 to patients' cells resulted in an upregulation of activation-specific cell surface antigens on autologous T cells and elevated levels of CD95 on lymphoma B cells. Although anti-CD95 antibody CH-11 failed to induce apoptosis in lymphoma cells, we provide evidence that B-CLL cell depletion by bscCD x CD3 is mediated at least in part by apoptosis via the caspase pathway.
Keywords:	Apoptosis, B-CLL, Bispecific Antibody, Immunotherapy
Source:	Leukemia
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Volume:	17
Number:	5
Page Range:	900-909
Date:	May 2003
Official Publication:	https://doi.org/10.1038/sj.leu.2402890
PubMed:	View item in PubMed

Repository Staff Only: item control page