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  • Title: Bispecific single-chain diabody-mediated killing of endoglin-positive endothelial cells by cytotoxic T lymphocytes.
    Author: Korn T, Müller R, Kontermann RE.
    Journal: J Immunother; 2004; 27(2):99-106. PubMed ID: 14770081.
    Abstract:
    We present a novel vascular tumor therapy approach based on lysing endothelial cells by cytotoxic T lymphocytes (CTLs). Retargeting of CTLs is achieved by a recombinant bispecific antibody molecule (bispecific single-chain diabody) directed against human endoglin (CD105, EDG) and the T-cell coreceptor CD3 (scDb EDGCD3). Bacterially expressed scDb EDGCD3 was able to bind to endoglin-expressing endothelial cells as well as CD3-expressing T lymphocytes. The single-chain diabody mediated killing of endothelial cells (HUVEC, HMEC) by activated cytotoxic T lymphocytes at picomolar concentrations, and cells not expressing endoglin were not affected. Because endoglin is up-regulated in the vasculature of many solid tumors, this antibody molecule should be capable of lysing tumor endothelial cells and thus destroying the vascular bed of the tumor.
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