The bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82131
Title:
The bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis.
Authors:
Jensen, M; Ernestus, K; Kemshead, John T; Klehr, M; Von Bergwelt-Baildon, M S; Schinköthe, T; Schultze, J L; Berthold, F
Abstract:
To target the neural cell adhesion molecule (NCAM, CD56) on neuroblastoma by T cell-based immunotherapy we have generated a bi-specific CD3 x NCAM antibody (OE-1). This antibody can be used to redirect T cells to NCAM+ cells. Expectedly, the antibody binds specifically to NCAM+ neuroblastoma cells and CD3+ T cells. OE-1 induces T cell activation, expansion and effector function in peripheral blood mononuclear cell (PBMC)-derived CD4+ and CD8+ T cells. T cell activation was shown to depend on the presence of normal natural killer (NK) cells in the culture. Interestingly, while PBMC- derived T cells were activated by OE-1, NK cells were almost completely depleted, suggesting that T cells activated by OE-1 deleted the NK cells. Activated CD4+ and CD8+ T cells differentiate into a larger CCR7+ central memory and a smaller CCR7- effector memory cell population. Most importantly, preactivated T cells were highly cytotoxic for neuroblastoma cells. In eight of 11 experiments tumour-directed cytotoxicity was enhanced when NK cells were present during preactivation with OE-1. These data strongly support a bi-phasic therapeutic concept of primarily stimulating T cells with the bi-specific antibody in the presence of normal NCAM+ cells to induce T cell activation, migratory capacity and finally tumour cell lysis.
Affiliation:
Department of Pediatric Oncology and Hematology, University of Cologne, Germany. jensen@uni-koeln.de
Citation:
The bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis. 2003, 134 (2):253-63 Clin. Exp. Immunol.
Journal:
Clinical and Experimental Immunology
Issue Date:
Nov-2003
URI:
http://hdl.handle.net/10541/82131
DOI:
10.1046/j.1365-2249.2003.02300.x
PubMed ID:
14616785
Type:
Article
Language:
en
ISSN:
0009-9104
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJensen, M-
dc.contributor.authorErnestus, K-
dc.contributor.authorKemshead, John T-
dc.contributor.authorKlehr, M-
dc.contributor.authorVon Bergwelt-Baildon, M S-
dc.contributor.authorSchinköthe, T-
dc.contributor.authorSchultze, J L-
dc.contributor.authorBerthold, F-
dc.date.accessioned2009-09-22T15:59:34Z-
dc.date.available2009-09-22T15:59:34Z-
dc.date.issued2003-11-
dc.identifier.citationThe bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis. 2003, 134 (2):253-63 Clin. Exp. Immunol.en
dc.identifier.issn0009-9104-
dc.identifier.pmid14616785-
dc.identifier.doi10.1046/j.1365-2249.2003.02300.x-
dc.identifier.urihttp://hdl.handle.net/10541/82131-
dc.description.abstractTo target the neural cell adhesion molecule (NCAM, CD56) on neuroblastoma by T cell-based immunotherapy we have generated a bi-specific CD3 x NCAM antibody (OE-1). This antibody can be used to redirect T cells to NCAM+ cells. Expectedly, the antibody binds specifically to NCAM+ neuroblastoma cells and CD3+ T cells. OE-1 induces T cell activation, expansion and effector function in peripheral blood mononuclear cell (PBMC)-derived CD4+ and CD8+ T cells. T cell activation was shown to depend on the presence of normal natural killer (NK) cells in the culture. Interestingly, while PBMC- derived T cells were activated by OE-1, NK cells were almost completely depleted, suggesting that T cells activated by OE-1 deleted the NK cells. Activated CD4+ and CD8+ T cells differentiate into a larger CCR7+ central memory and a smaller CCR7- effector memory cell population. Most importantly, preactivated T cells were highly cytotoxic for neuroblastoma cells. In eight of 11 experiments tumour-directed cytotoxicity was enhanced when NK cells were present during preactivation with OE-1. These data strongly support a bi-phasic therapeutic concept of primarily stimulating T cells with the bi-specific antibody in the presence of normal NCAM+ cells to induce T cell activation, migratory capacity and finally tumour cell lysis.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subject.meshAntibodies, Bispecific-
dc.subject.meshAntibody Specificity-
dc.subject.meshAntigens, CD3-
dc.subject.meshCD4-Positive T-Lymphocytes-
dc.subject.meshCD8-Positive T-Lymphocytes-
dc.subject.meshCell Division-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCytotoxicity, Immunologic-
dc.subject.meshHumans-
dc.subject.meshKiller Cells, Natural-
dc.subject.meshLymphocyte Activation-
dc.subject.meshNeural Cell Adhesion Molecules-
dc.subject.meshNeuroblastoma-
dc.subject.meshT-Lymphocytes-
dc.titleThe bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatric Oncology and Hematology, University of Cologne, Germany. jensen@uni-koeln.deen
dc.identifier.journalClinical and Experimental Immunologyen
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