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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-5-16
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0887-6924
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pubmed:author |
pubmed-author:BaeuerleP APA,
pubmed-author:BargouR CRC,
pubmed-author:BommertKK,
pubmed-author:DörkenBB,
pubmed-author:DreierTT,
pubmed-author:GruenMM,
pubmed-author:HanakamFF,
pubmed-author:KarawajewLL,
pubmed-author:KubátRR,
pubmed-author:LöfflerAA,
pubmed-author:SchrieverFF,
pubmed-author:WuchterCC
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
900-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12750704-Aged,
pubmed-meshheading:12750704-Aged, 80 and over,
pubmed-meshheading:12750704-Annexin A5,
pubmed-meshheading:12750704-Antibodies, Bispecific,
pubmed-meshheading:12750704-Antibody Specificity,
pubmed-meshheading:12750704-Antigens, CD19,
pubmed-meshheading:12750704-Antigens, CD3,
pubmed-meshheading:12750704-B-Lymphocytes,
pubmed-meshheading:12750704-Caspases,
pubmed-meshheading:12750704-Cell Death,
pubmed-meshheading:12750704-Cell Division,
pubmed-meshheading:12750704-Cytotoxicity, Immunologic,
pubmed-meshheading:12750704-Enzyme Activation,
pubmed-meshheading:12750704-Female,
pubmed-meshheading:12750704-Flow Cytometry,
pubmed-meshheading:12750704-Humans,
pubmed-meshheading:12750704-Immunotherapy,
pubmed-meshheading:12750704-Interleukin-2,
pubmed-meshheading:12750704-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:12750704-Leukocytes, Mononuclear,
pubmed-meshheading:12750704-Lymphocyte Depletion,
pubmed-meshheading:12750704-Male,
pubmed-meshheading:12750704-Middle Aged,
pubmed-meshheading:12750704-T-Lymphocytes,
pubmed-meshheading:12750704-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct.
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pubmed:affiliation |
Department of Haematology, Oncology and Tumourimmunology, Robert Rössle Clinic, Charité, Humboldt University of Berlin, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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