Schneider, M. A. and Bruehl, H. and Wechselberger, A. and Cihak, J. and Stangassinger, M. and Schloendorff, D. and Mack, Matthias (2005) In vitro and in vivo properties of a dimeric bispecific single-chain antibody IgG-fusion protein for depletion of CCR2(+) target cells in mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 35 (3). pp. 987-995. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
The chemokine receptor CCR2 is highly expressed on leukocytes in several inflammatory diseases of both mice and men. Apart from blockade of CCR2 to prevent chemokine-dependent cell migration, depletion of CCR2(+) cells might be a promising strategy for treatment of inflammatory diseases. We therefore designed a bispecific antibody construct with the ability to deplete CCR2(+) target cells in vitro and in vivo. The bispecific antibody construct consists of two single-chain antibody variable fragments (scFv) - one recognizing murine CD3 epsilon and the other recognizing murine CCR2 -joined by a short linker and fused to a modified hinge region and the C(H)2 and C(H)3 domains of murine IgG1 for dimerization. The protein was expressed in mammalian cells and purified via its C-terminal histidine tail. In vitro this construct leads to efficient antigen specific and costimulation-independent activation of T cells and strong lysis of CCR2(+) target cells. In vivo the construct induces an almost complete depletion of CCR2(+)CD11b(+) monocytes from the peripheral blood and spleens of BALB/c mice within 24 h. This recombinant protein construct is a dimeric, bispecific antibody with markedly improved serum levels compared to conventional bispecific single-chain antibodies and the ability to deplete CCR2(+)CD11b(+) monocytes in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RENAL-TRANSPLANT REJECTION; CHEMOKINE RECEPTORS; TANDEM DIABODY; CC-CHEMOKINE; T-CELLS; EXPRESSION; CYTOTOXICITY; ARTHRITIS; DISEASES; PHARMACOKINETICS; bispecific single-chain antibody; antibody engineering; chemokine receptor; CCR2; cell depletion |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2021 10:44 |
| Last Modified: | 18 May 2021 10:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36404 |
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