Krippner-Heidenreich, Anja and Grunwald, Ingo and Zimmermann, Gudrun and Kuehnle, Marie and Gerspach, Jeannette and Sterns, Theobald and Shnyder, Steve D. and Gill, Jason H. and Maennel, Daniela N. and Pfizenmaier, Klaus and Scheurich, Peter (2008) Single-chain TNF, a TNF derivative with enhanced stability and antitumoral activity. JOURNAL OF IMMUNOLOGY, 180 (12). pp. 8176-8183. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
The inflammatory and proapoptotic cytokine TNF possesses a compelling potential as an antitumoral therapeutic agent. Possible target cells include the malignant cells themselves, the tumor vasculature, or the immune system. As the clinical use of TNF is limited by systemic toxicity, targeting strategies using TNF-based fusion proteins are currently used. A major obstacle, however, is that homotrimeric TNF ligands are prone to activity loss due to dissociation into their monomers. In this study, we report the construction of single-chain TNF molecule, a TNF mutant consisting of three TNF monomers fused by short peptide linkers. In comparison to wild-type TNF, single-chain TNF was found to possess increased stability in vitro and in vivo, displayed reduced systemic toxicity yet slightly enhanced antitumoral activity in mouse models. Creation of single-chain variants is a new approach for improvement of functional activity of therapeutics based on TNF family ligands.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; MOLECULAR-DYNAMICS; SIGNALING COMPLEX; RECEPTOR; APOPTOSIS; BIOACTIVITY; MUTANTS; PROTEIN; LIGAND; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 08:10 |
| Last Modified: | 29 Oct 2020 08:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30732 |
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