ABSTRACTThe development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated “Fc-one/kappa” (Fc1$\kappa$) is based on interspersed constant Ig domains substituting the CH3 domains of a $\gamma$1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CL$\kappa$ domains and contain ...
%0 Journal Article
%1 Richter2019
%A Richter, Fabian
%A Seifert, Oliver
%A Herrmann, Andreas
%A Pfizenmaier, Klaus
%A Kontermann, Roland E.
%D 2019
%I Taylor & Francis
%J mAbs
%K 2019 izi kontermann pfizenmaier
%P 1--13
%R 10.1080/19420862.2019.1596512
%T Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc
%U https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1596512
%X ABSTRACTThe development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated “Fc-one/kappa” (Fc1$\kappa$) is based on interspersed constant Ig domains substituting the CH3 domains of a $\gamma$1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CL$\kappa$ domains and contain ...
@article{Richter2019,
abstract = {ABSTRACTThe development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory responses mediated by TNF while leaving regenerative and pro-survival signals transduced by TNFR2 untouched. We recently generated a monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient inhibitor of TNFR1. To improve the pharmacokinetic properties of Fab 13.7, the variable domains of the heavy and light chains were fused to the N-termini of newly generated heterodimerizing Fc chains. This novel Fc heterodimerization technology, designated “Fc-one/kappa” (Fc1$\kappa$) is based on interspersed constant Ig domains substituting the CH3 domains of a $\gamma$1 Fc. The interspersed immunoglobulin (Ig) domains originate from the per se heterodimerizing constant CH1 and CL$\kappa$ domains and contain ...},
added-at = {2019-04-01T11:58:16.000+0200},
author = {Richter, Fabian and Seifert, Oliver and Herrmann, Andreas and Pfizenmaier, Klaus and Kontermann, Roland E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2a0dc33a6d1a0e17bf66734ff4bff080a/cristiano},
doi = {10.1080/19420862.2019.1596512},
interhash = {606a533e05778b0b1c8fa13e058ca67f},
intrahash = {a0dc33a6d1a0e17bf66734ff4bff080a},
issn = {1942-0862},
journal = {mAbs},
keywords = {2019 izi kontermann pfizenmaier},
month = mar,
pages = {1--13},
publisher = {Taylor {\&} Francis},
timestamp = {2019-04-01T09:58:16.000+0200},
title = {{Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc}},
url = {https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1596512},
year = 2019
}
