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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-05

AUTHORS

A Löffler, M Gruen, C Wuchter, F Schriever, P Kufer, T Dreier, F Hanakam, P A Baeuerle, K Bommert, L Karawajew, B Dörken, R C Bargou

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 bscCD3 x CD3 is mediated at least in part by apoptosis via the caspase pathway. More... »

PAGES

2402890

Journal

TITLE

Leukemia

ISSUE

5

VOLUME

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2402890

DOI

http://dx.doi.org/10.1038/sj.leu.2402890

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000138204

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12750704


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