Show simple item record

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.
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
html.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.


This item appears in the following Collection(s)

Show simple item record