%0 Journal Article %1 Gerspach2006a %A Gerspach, Jeannette %A Németh, Julia %A Münkel, Sabine %A Wajant, Harald %A Pfizenmaier, Klaus %D 2006 %J Cancer Immunology, Immunotherapy %K 2006 izi pfizenmaier %N 12 %P 1590--1600 %R 10.1007/s00262-006-0162-6 %T Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface %U https://www.ncbi.nlm.nih.gov/pubmed/16636812 %V 55 %X We have previously developed TNF prodrugs comprised of a N-terminal scFv targeting, a TNF effector and a C-terminal TNFR1-derived inhibitor module linked to TNF via a MMP-2 motif containing peptide, allowing activation by MMP-2-expressing tumor cells. To overcome the known heterogeneity of matrix metalloprotease expression, we developed TNF prodrugs that become processed by other tumor and/or stroma-associated proteases. These TNF prodrugs comprise either an uPA-selective or a dual uPA-MMP-2-specific linker which displayed efficient, target-dependent and cleavage sequence-specific activation by the corresponding tumor cell-expressed proteases. Selective pharmacologic inhibition of endogenous uPA and MMP-2 confirm independent prodrug processing by these two model proteases and indicate the functional superiority of a prodrug containing a multi-specific protease linker. Processing optimised TNF prodrugs should increase the proportion of active therapeutic within the targeted tissue and thus potentially enhance tumor response rate. %Z Gerspach, JeannetteNemeth, JuliaMunkel, SabineWajant, HaraldPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tGermanyCancer Immunol Immunother. 2006 Dec;55(12):1590-600. doi: 10.1007/s00262-006-0162-6. Epub 2006 Apr 25. %7 2006/04/26 %@ 0340-7004 (Print) 0340-7004 (Linking)

@article{Gerspach2006a, abstract = {We have previously developed TNF prodrugs comprised of a N-terminal scFv targeting, a TNF effector and a C-terminal TNFR1-derived inhibitor module linked to TNF via a MMP-2 motif containing peptide, allowing activation by MMP-2-expressing tumor cells. To overcome the known heterogeneity of matrix metalloprotease expression, we developed TNF prodrugs that become processed by other tumor and/or stroma-associated proteases. These TNF prodrugs comprise either an uPA-selective or a dual uPA-MMP-2-specific linker which displayed efficient, target-dependent and cleavage sequence-specific activation by the corresponding tumor cell-expressed proteases. Selective pharmacologic inhibition of endogenous uPA and MMP-2 confirm independent prodrug processing by these two model proteases and indicate the functional superiority of a prodrug containing a multi-specific protease linker. Processing optimised TNF prodrugs should increase the proportion of active therapeutic within the targeted tissue and thus potentially enhance tumor response rate.}, added-at = {2023-06-29T13:07:55.000+0200}, annote = {Gerspach, JeannetteNemeth, JuliaMunkel, SabineWajant, HaraldPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tGermanyCancer Immunol Immunother. 2006 Dec;55(12):1590-600. doi: 10.1007/s00262-006-0162-6. Epub 2006 Apr 25.}, author = {Gerspach, Jeannette and N{\'{e}}meth, Julia and M{\"{u}}nkel, Sabine and Wajant, Harald and Pfizenmaier, Klaus}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2299fd46a15b204ca58f6b766b2db30f6/fabian}, doi = {10.1007/s00262-006-0162-6}, edition = {2006/04/26}, interhash = {c33839b86c42507b9337232e749f9e2d}, intrahash = {299fd46a15b204ca58f6b766b2db30f6}, isbn = {0340-7004 (Print) 0340-7004 (Linking)}, issn = {03407004}, journal = {Cancer Immunology, Immunotherapy}, keywords = {2006 izi pfizenmaier}, number = 12, pages = {1590--1600}, pmid = {16636812}, timestamp = {2023-06-29T13:07:55.000+0200}, title = {{Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface}}, url = {https://www.ncbi.nlm.nih.gov/pubmed/16636812}, volume = 55, year = 2006 }