The bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis.
Kemshead, John T
Von Bergwelt-Baildon, M S
Schultze, J L
AffiliationDepartment of Pediatric Oncology and Hematology, University of Cologne, Germany. firstname.lastname@example.org
MetadataShow full item record
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.
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.
JournalClinical and Experimental Immunology
- A bispecific single-chain antibody directed against EpCAM/CD3 in combination with the cytokines interferon alpha and interleukin-2 efficiently retargets T and CD3+CD56+ natural-killer-like T lymphocytes to EpCAM-expressing tumor cells.
- Authors: Flieger D, Kufer P, Beier I, Sauerbruch T, Schmidt-Wolf IG
- Issue date: 2000 Oct
- Unprimed CD4+ and CD8+ T cells can be rapidly activated by a CD3 x CD19 bispecific antibody to proliferate and become cytotoxic.
- Authors: Haagen IA, de Lau WB, Bast BJ, Geerars AJ, Clark MR, de Gast BC
- Issue date: 1994 Dec
- Systematic characterization of human CD8+ T cells with natural killer cell markers in comparison with natural killer cells and normal CD8+ T cells.
- Authors: Ohkawa T, Seki S, Dobashi H, Koike Y, Habu Y, Ami K, Hiraide H, Sekine I
- Issue date: 2001 Jul
- Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells.
- Authors: Fan D, Li W, Yang Y, Zhang X, Zhang Q, Yan Y, Yang M, Wang J, Xiong D
- Issue date: 2015 Oct 6
- Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity.
- Authors: Hombach A, Tillmann T, Jensen M, Heuser C, Sircar R, Diehl V, Kruis W, Pohl C
- Issue date: 1997 May