ABSTRACTCo-stimulatory signals induced by ligands of the tumor necrosis factor superfamily (TNFSF) play a central role in T cell activation and have emerged as a promising strategy in cancer immunotherapy. Here, we established a novel class of bifunctional co-stimulatory fusion proteins with the aim to boost T cell activation at the level of T cell – antigen-presenting cell (APC) interaction. These novel dual-acting cytokine fusion proteins were created by connecting two different homotrimeric TNFSF ligands to form homotrimeric bifunctional molecules (Duokines) or by connecting single-chain derivatives of two different homotrimeric TNFSF with a single, flexible linker (single-chain Duokines, scDuokines). By linking the TNFSF ligands 4-1BBL, OX40L and CD27L in all possible combinations, cis-acting Duokines were generated that act on the same or adjacent T cells, while combining CD40L with 4-1BBL, OX40L and CD27L resulted in trans-acting Duokines acting simultaneously on APCs and T cells. In vitro, co-stimu...
%0 Journal Article
%1 Fellermeier-Kopf2018
%A Fellermeier-Kopf, Sina
%A Gieseke, Friederike
%A Sahin, Ugur
%A Müller, Dafne
%A Pfizenmaier, Klaus
%A Kontermann, Roland E.
%D 2018
%I Taylor & Francis
%J OncoImmunology
%K 2018 izi kontermann
%N 9
%P e1471442
%R 10.1080/2162402X.2018.1471442
%T Duokines: a novel class of dual-acting co-stimulatory molecules acting in cis or trans
%U https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1471442
%V 7
%X ABSTRACTCo-stimulatory signals induced by ligands of the tumor necrosis factor superfamily (TNFSF) play a central role in T cell activation and have emerged as a promising strategy in cancer immunotherapy. Here, we established a novel class of bifunctional co-stimulatory fusion proteins with the aim to boost T cell activation at the level of T cell – antigen-presenting cell (APC) interaction. These novel dual-acting cytokine fusion proteins were created by connecting two different homotrimeric TNFSF ligands to form homotrimeric bifunctional molecules (Duokines) or by connecting single-chain derivatives of two different homotrimeric TNFSF with a single, flexible linker (single-chain Duokines, scDuokines). By linking the TNFSF ligands 4-1BBL, OX40L and CD27L in all possible combinations, cis-acting Duokines were generated that act on the same or adjacent T cells, while combining CD40L with 4-1BBL, OX40L and CD27L resulted in trans-acting Duokines acting simultaneously on APCs and T cells. In vitro, co-stimu...
@article{Fellermeier-Kopf2018,
abstract = {ABSTRACTCo-stimulatory signals induced by ligands of the tumor necrosis factor superfamily (TNFSF) play a central role in T cell activation and have emerged as a promising strategy in cancer immunotherapy. Here, we established a novel class of bifunctional co-stimulatory fusion proteins with the aim to boost T cell activation at the level of T cell – antigen-presenting cell (APC) interaction. These novel dual-acting cytokine fusion proteins were created by connecting two different homotrimeric TNFSF ligands to form homotrimeric bifunctional molecules (Duokines) or by connecting single-chain derivatives of two different homotrimeric TNFSF with a single, flexible linker (single-chain Duokines, scDuokines). By linking the TNFSF ligands 4-1BBL, OX40L and CD27L in all possible combinations, cis-acting Duokines were generated that act on the same or adjacent T cells, while combining CD40L with 4-1BBL, OX40L and CD27L resulted in trans-acting Duokines acting simultaneously on APCs and T cells. In vitro, co-stimu...},
added-at = {2018-09-17T11:08:07.000+0200},
author = {Fellermeier-Kopf, Sina and Gieseke, Friederike and Sahin, Ugur and M{\"{u}}ller, Dafne and Pfizenmaier, Klaus and Kontermann, Roland E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/259b759510ea9e2b43c9ecf0a9b585465/cristiano},
doi = {10.1080/2162402X.2018.1471442},
interhash = {81f4496bbbc94d33c34ca45771c5de20},
intrahash = {59b759510ea9e2b43c9ecf0a9b585465},
issn = {2162-402X},
journal = {OncoImmunology},
keywords = {2018 izi kontermann},
month = sep,
number = 9,
pages = {e1471442},
publisher = {Taylor {\&} Francis},
timestamp = {2019-01-17T12:17:58.000+0100},
title = {{Duokines: a novel class of dual-acting co-stimulatory molecules acting in cis or trans}},
url = {https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1471442},
volume = 7,
year = 2018
}
