Toggle Main Menu Toggle Search

Open Access padlockePrints

Single-Chain TNF, a TNF Derivative with Enhanced Stability and Antitumoral Activity

Lookup NU author(s): Dr Anja Krippner-Heidenreich, Dr Jason GillORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Krippner-Heidenreich A, Grunwald I, Zimmermann G, Kühnle M, Gerspach J, Sterns T, Shnyder SD, Gill JH, Männel DN, Pfizenmaier K, Scheurich P

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 2008

Volume: 180

Issue: 12

Pages: 8176-8183

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists