{ "types" : { "Bookmark" : { "pluralLabel" : "Bookmarks" }, "Publication" : { "pluralLabel" : "Publications" }, "GoldStandardPublication" : { "pluralLabel" : "GoldStandardPublications" }, "GoldStandardBookmark" : { "pluralLabel" : "GoldStandardBookmarks" }, "Tag" : { "pluralLabel" : "Tags" }, "User" : { "pluralLabel" : "Users" }, "Group" : { "pluralLabel" : "Groups" }, "Sphere" : { "pluralLabel" : "Spheres" } }, "properties" : { "count" : { "valueType" : "number" }, "date" : { "valueType" : "date" }, "changeDate" : { "valueType" : "date" }, "url" : { "valueType" : "url" }, "id" : { "valueType" : "url" }, "tags" : { "valueType" : "item" }, "user" : { "valueType" : "item" } }, "items" : [ { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20bc51887900eea0db763789a4dbfb3d5/pumaizi", "tags" : [ "2008","izi","kontermann" ], "intraHash" : "0bc51887900eea0db763789a4dbfb3d5", "interHash" : "8551110d221ec17c9b29a7f85d3b481a", "label" : "Novel single-chain Fv\u2032 formats for the generation of immunoliposomes by site-directed coupling", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Bioconjugate Chemistry", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17988079", "author": [ "S. K E Messerschmidt","Anke Kolbe","Dafne Müller","Michael Knoll","Jürgen Pleiss","Roland E. Kontermann" ], "authors": [ {"first" : "S. K E", "last" : "Messerschmidt"}, {"first" : "Anke", "last" : "Kolbe"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Michael", "last" : "Knoll"}, {"first" : "Jürgen", "last" : "Pleiss"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "19","number": "1","pages": "362--369","abstract": "Immunoliposomes generated by coupling of antibodies to the liposomal surface allow for an active targeting of entrapped compounds to diseased areas. Single-chain Fv fragments (scFv) represent the smallest part of an antibody containing the entire antigen-binding site. They can be coupled in a defined and site-directed manner through genetically engineered cysteine residues, for example, those added at the C-terminus. Here, we have performed a comparative analysis of various scFv' variants with cysteine residues present at the end of a C-terminal extension of varying length and composition (HC variants) or introduced in the linker sequence connecting the variable heavy and light chain domain (LC variants). Using a scFv fragment directed against fibroblast activation protein (FAP) as a model antibody, we could show that all variants can be employed for the generation of active immunoliposomes, although the presence of three additional cysteine residues in one scFv' molecule resulted in decreased binding of immunoliposomes compared to that of immunoliposomes generated with scFv' molecules containing only one additional cysteine residue. In order to further improve the scFv' format by reducing the number of additional amino acid residues, we also generated molecules with the hexahistidyl-tag incorporated into the linker sequence together with a cysteine residue either at position 1 or 3 of the linker sequence (LCH variants). These newly designed scFv' molecules may be particularly suitable for the generation of immunoliposomes and other antibody conjugates, limiting the number of additional residues in these antibody molecules to a minimum.", "isbn" : "1043-1802 (Print)$\\backslash$r1043-1802 (Linking)", "pmid" : "17988079", "issn" : "10431802", "doi" : "10.1021/bc700349k", "bibtexKey": "Messerschmidt2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/262b5baf9787ee1c928e4f871eabef5c2/pumaizi", "tags" : [ "2008","izi","hausser" ], "intraHash" : "62b5baf9787ee1c928e4f871eabef5c2", "interHash" : "32f4758e2b7a5c153c0e4f339aae6ae0", "label" : "Yeast and human Ysl2p/hMon2 interact with Gga adaptors and mediate their subcellular distribution", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "EMBO Journal", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18418388", "author": [ "Birgit Singer-Krüger","Maja Lasić","Anna Maria Bürger","Angelika Haußer","Rüdiger Pipkorn","Yi Wang" ], "authors": [ {"first" : "Birgit", "last" : "Singer-Krüger"}, {"first" : "Maja", "last" : "Lasić"}, {"first" : "Anna Maria", "last" : "Bürger"}, {"first" : "Angelika", "last" : "Haußer"}, {"first" : "Rüdiger", "last" : "Pipkorn"}, {"first" : "Yi", "last" : "Wang"} ], "volume": "27","number": "10","pages": "1423--1435","abstract": "The Gga proteins represent a family of ubiquitously expressed clathrin adaptors engaged in vesicle budding at the tubular endosomal network/trans Golgi network. Their membrane recruitment is commonly thought to involve interactions with Arf and signals in cargo through the so-called VHS domain. For yeast Gga proteins, however, partners binding to its VHS domain have remained elusive and Gga localization does not absolutely depend on Arf. Here, we demonstrate that yeast Gga recruitment relies on a network of interactions between the scaffold Ysl2p/Mon2p, the small GTPase Arl1p, and the flippase Neo1p. Deletion of either YSL2 or ARL1 causes mislocalization of Gga2p, whereas a neo1-69 mutant accumulates Gga2p on aberrant structures. Remarkably, Ysl2p directly interacts with human and yeast Ggas through the VHS domain, and binding to Gga proteins is also found for the human Ysl2p orthologue hMon2. Thus, Ysl2p represents an essential, evolutionarily conserved member of a network controlling direct binding and membrane docking of Ggas. Because activated Arl1p is part of the network that binds Gga2p, Arf and Arf-like GTPases may interact in a regulatory cascade.", "isbn" : "1460-2075 (Electronic)$\\backslash$r0261-4189 (Linking)", "pmid" : "18418388", "issn" : "02614189", "doi" : "10.1038/emboj.2008.75", "bibtexKey": "Singer-Kruger2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/24310eff0a35774c04e13ef2bda218716/pumaizi", "tags" : [ "2008","izi","pfizenmaier","hausser" ], "intraHash" : "4310eff0a35774c04e13ef2bda218716", "interHash" : "248932eadbce2656de5e225cc4c8d1a4", "label" : "Expression patterns of protein kinase D 3 during mouse development", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "BMC Developmental Biology", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18439271", "author": [ "Kornelia Ellwanger","Klaus Pfizenmaier","Sylke Lutz","Angelika Hausser" ], "authors": [ {"first" : "Kornelia", "last" : "Ellwanger"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Sylke", "last" : "Lutz"}, {"first" : "Angelika", "last" : "Hausser"} ], "volume": "8","pages": "47","abstract": "BACKGROUND: The PKD family of serine/threonine kinases comprises a single member in Drosophila (dPKD), two isoforms in C. elegans (DKF-1 and 2) and three members, PKD1, PKD2 and PKD3 in mammals. PKD1 and PKD2 have been the focus of most studies up to date, which implicate these enzymes in very diverse cellular functions, including Golgi organization and plasma membrane directed transport, immune responses, apoptosis and cell proliferation. Concerning PKD3, a role in the formation of vesicular transport carriers at the trans-Golgi network (TGN) and in basal glucose transport has been inferred from in vitro studies. So far, however, the physiological functions of the kinase during development remain unknown. RESULTS: We have examined the expression pattern of PKD3 during the development of mouse embryos by immunohistochemistry. Using a PKD3 specific antibody we demonstrate that the kinase is differentially expressed during organogenesis. In the developing heart a strong PKD3 expression is constantly detected from E10 to E16.5. From E12.5 on PKD3 is increasingly expressed in neuronal as well as in the supporting connective tissue and in skeletal muscles. CONCLUSION: The data presented support an important role for PKD3 during development of these tissues.", "isbn" : "1471-213X (Electronic)\n1471-213X (Linking)", "pmid" : "18439271", "issn" : "1471213X", "doi" : "10.1186/1471-213X-8-47", "bibtexKey": "Ellwanger2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2d55fc50c1990a01d7035a48d29e09b69/pumaizi", "tags" : [ "2008","izi","mueller","kontermann" ], "intraHash" : "d55fc50c1990a01d7035a48d29e09b69", "interHash" : "b66204619f50db27333edd3e204114fb", "label" : "A novel antibody-4-1BBL fusion protein for targeted costimulation in cancer immunotherapy", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Immunotherapy", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18779748", "author": [ "Dafne Müller","Katharina Frey","Roland E. Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Katharina", "last" : "Frey"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "31","number": "8","pages": "714--722","abstract": "Costimulation is an essential step in T-cell activation and hence, represents an important aspect in cancer immunotherapy. 4-1BB, a member of the tumor necrosis factor receptor family, has gained particular interest as a costimulatory molecule. Here, we investigated the potential of a targeted activation of 4-1BB-mediated costimulation at the tumor site by generating a recombinant antibody-cytokine fusion protein composed of a single-chain antibody fragment (scFv36) specific for the tumor stromal antigen fibroblast activation protein (FAP) and the extracellular domain of the 4-1BB ligand (4-1BBL). The scFv36-4-1BBL fusion protein is a homotrimeric molecule that binds specifically to FAP and the receptor 4-1BB. T-cell costimulation was demonstrated by interferon-gamma release of peripheral blood mononuclear cells cocultured with FAP-expressing HT1080 cells upon T-cell receptor triggering by monoclonal anti-CD3 antibody. Costimulatory activity of the scFv36-4-1BBL fusion protein was concentration dependent, ligand-specific, and substantially constrained to FAP-expressing target cell binding. Furthermore, scFv36-4-1BBL enhanced T-cell activation when the bispecific antibody scDb33CD3 (specific for FAP and CD3) was used as primary stimulus. Thus, target cell-dependent costimulation with scFv36-4-1BBL constitutes a new option to enhance T-cell activation by bispecific antibodies or antigen-dependent T-cell receptor triggering and should be useful to improve T cell-mediated antitumor responses.", "isbn" : "1537-4513 (Electronic)$\\backslash$r1524-9557 (Linking)", "pmid" : "18779748", "issn" : "15249557", "doi" : "10.1097/CJI.0b013e31818353e9", "bibtexKey": "Muller2008b" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e6a0e2fb54a9a9e445f8b74d2d25d18a/pumaizi", "tags" : [ "2008","olayioye","izi","hausser" ], "intraHash" : "e6a0e2fb54a9a9e445f8b74d2d25d18a", "interHash" : "f3e842c2d79b97dc2d2b729b7a0d82a1", "label" : "DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of cell science", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19066281", "author": [ "Rolf-Peter Scholz","Jennifer Regner","Anke Theil","Patrik Erlmann","Gerlinde Holeiter","Ruth Jähne","Simone Schmid","Angelika Hausser","Monilola a Olayioye" ], "authors": [ {"first" : "Rolf-Peter", "last" : "Scholz"}, {"first" : "Jennifer", "last" : "Regner"}, {"first" : "Anke", "last" : "Theil"}, {"first" : "Patrik", "last" : "Erlmann"}, {"first" : "Gerlinde", "last" : "Holeiter"}, {"first" : "Ruth", "last" : "Jähne"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Monilola a", "last" : "Olayioye"} ], "volume": "122","number": "Pt 1","pages": "92--102","abstract": "Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.", "isbn" : "0021-9533 (Print)$\\backslash$n0021-9533 (Linking)", "pmid" : "19066281", "issn" : "0021-9533", "doi" : "10.1242/jcs.036251", "bibtexKey": "Scholz2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2871b77201c953dadd9fc026efafd703c/pumaizi", "tags" : [ "2008","izi" ], "intraHash" : "871b77201c953dadd9fc026efafd703c", "interHash" : "c87d1d21ae65ffab6a251854dee116bc", "label" : "Combined Inhibition of MAPK and mTOR Signaling Inhibits Growth, Induces Cell Death, and Abrogates Invasive Growth of Melanoma Cells", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Investigative Dermatology","publisher":"Elsevier BV", "year": "2008", "url": "https://doi.org/10.1038%2Fjid.2008.44", "author": [ "Konstantinos G. Lasithiotakis","Tobias W. Sinnberg","Birgit Schittek","Keith T. Flaherty","Dagmar Kulms","Evelyn Maczey","Claus Garbe","Friedegund E. Meier" ], "authors": [ {"first" : "Konstantinos G.", "last" : "Lasithiotakis"}, {"first" : "Tobias W.", "last" : "Sinnberg"}, {"first" : "Birgit", "last" : "Schittek"}, {"first" : "Keith T.", "last" : "Flaherty"}, {"first" : "Dagmar", "last" : "Kulms"}, {"first" : "Evelyn", "last" : "Maczey"}, {"first" : "Claus", "last" : "Garbe"}, {"first" : "Friedegund E.", "last" : "Meier"} ], "volume": "128","number": "8","pages": "2013--2023", "doi" : "10.1038/jid.2008.44", "bibtexKey": "Lasithiotakis_2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2d75239a53149873995fdeebcab822e0c/pumaizi", "tags" : [ "2008","izi","kontermann" ], "intraHash" : "d75239a53149873995fdeebcab822e0c", "interHash" : "2d8e2a5eff6769723d0fd0abae468c74", "label" : "N-glycosylation as novel strategy to improve pharmacokinetic properties of bispecific single-chain diabodies", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18211902", "author": [ "Roland Stork","Kirstin A. Zettlitz","Dafne Müller","Miriam Rether","Franz Georg Hanisch","Roland E. Kontermann" ], "authors": [ {"first" : "Roland", "last" : "Stork"}, {"first" : "Kirstin A.", "last" : "Zettlitz"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Miriam", "last" : "Rether"}, {"first" : "Franz Georg", "last" : "Hanisch"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "283","number": "12","pages": "7804--7812","abstract": "The therapeutic efficacy of recombinant antibodies such as single-chain Fv fragments and small bispecific or bifunctional molecules is often limited by rapid elimination from the circulation because of their small size. Here, we have investigated the effects of N-glycosylation on the activity and pharmacokinetics of a small bispecific single-chain diabody (scDb CEACD3) developed for the retargeting of cytotoxic T cells to CEA-expressing tumor cells. We could show that the introduction of N-glycosylation sequons into the flanking linker and a C-terminal extension results in the production of N-glycosylated molecules after expression in transfected HEK293 cells. N-Glycosylated scDb variants possessing 3, 6, or 9 N-glycosylation sites, respectively, retained antigen binding activity and bispecificity for target and effector cells as shown in a target cell-dependent IL-2 release assay, although activity was reduced approximately 3-5-fold compared with the unmodified scDb. All N-glycosylated scDb variants exhibited a prolonged circulation time compared with scDb, leading to a 2-3-fold increase of the area under curve (AUC). In comparison, conjugation of a branched 40-kDa PEG chain increased AUC by a factor of 10.6, while a chimeric anti-CEA IgG1 molecule had the longest circulation time with a 17-fold increase in AUC. Thus, N-glycosylation complements the repertoire of strategies to modulate pharmacokinetics of small recombinant antibody molecules by an approach that moderately prolongs circulation time.", "isbn" : "4971168567", "pmid" : "18211902", "issn" : "00219258", "doi" : "10.1074/jbc.M709179200", "bibtexKey": "Stork2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/269bbcf3fa7906c44b6eecc00d362a62e/pumaizi", "tags" : [ "2008","izi","mueller","kontermann" ], "intraHash" : "69bbcf3fa7906c44b6eecc00d362a62e", "interHash" : "bcd2e5cf5d41ed877a04ca196828703e", "label" : "Murine endoglin-specific single-chain Fv fragments for the analysis of vascular targeting strategies in mice", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Immunological Methods", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18790696", "author": [ "Dafne Müller","Gerhard Trunk","Anke Sichelstiel","Kirstin A. Zettlitz","Miguel Quintanilla","Roland E. Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Gerhard", "last" : "Trunk"}, {"first" : "Anke", "last" : "Sichelstiel"}, {"first" : "Kirstin A.", "last" : "Zettlitz"}, {"first" : "Miguel", "last" : "Quintanilla"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "339","number": "1","pages": "90--98","abstract": "Endoglin has been identified as a promising cell surface antigen for vascular targeting approaches in cancer therapy, e.g. employing antibody molecules as targeting moieties. However, in vivo analysis of such strategies in mouse models requires antibodies recognizing endoglin on mouse endothelial cells. Here we describe the isolation of single-chain Fv fragments (scFvs) from phage display libraries, which bind to the extracellular region of mouse endoglin. One of these clones, scFv mE12, showed strong (Kd= 11 nM) and selective binding to purified endoglin and also to the endoglin-expressing mouse endothelioma cell line eEnd.2. This antibody recognized a linear epitope located in the N-terminal region (aa 27-361) of endoglin. Cell binding was further increased by generating a bivalent scFv-Fc fusion protein composed of scFv mE12 and the human $\\gamma$1 Fc part. Moreover, scFv mE12 was endowed with an additional cysteine residue in the linker region and applied for the generation of anti-endoglin scFv immunoliposomes capable of selectively binding to endoglin-expressing cells. Thus, anti-mouse endoglin scFv mE12 should be useful to analyze vascular targeting strategies in mice. © 2008 Elsevier B.V. All rights reserved.", "isbn" : "0022-1759 (Print)$\\backslash$r0022-1759 (Linking)", "pmid" : "18790696", "issn" : "00221759", "doi" : "10.1016/j.jim.2008.08.008", "bibtexKey": "Muller2008c" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2206571ae572de8edb6e23d9f23f7f671/pumaizi", "tags" : [ "2008","izi","pfizenmaier" ], "intraHash" : "206571ae572de8edb6e23d9f23f7f671", "interHash" : "63e18d49440a43a192bcce45440c9d75", "label" : "Activity of soluble OX40 ligand is enhanced by oligomerization and cell surface immobilization", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "FEBS Journal", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18397322", "author": [ "Nicole Müller","Agnes Wyzgol","Sabine Münkel","Klaus Pfizenmaier","Harald Wajant" ], "authors": [ {"first" : "Nicole", "last" : "Müller"}, {"first" : "Agnes", "last" : "Wyzgol"}, {"first" : "Sabine", "last" : "Münkel"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Harald", "last" : "Wajant"} ], "volume": "275","number": "9","pages": "2296--2304","abstract": "OX40 ligand (OX40L) and OX40 are typical members of the tumor necrosis factor ligand family and the tumor necrosis factor receptor superfamily, respectively, and are involved in the costimulation and differentiation of T cells. Like other tumor necrosis factor ligands, OX40L is a type II transmembrane protein. Recombinant soluble human OX40L assembles into trimers and is practically inactive despite binding to OX40. However, oligomerization of soluble OX40L trimers by cross-linking with antibodies or by expression as a hexameric fusion protein strongly increased the activity of the ligand. Moreover, a fusion protein of OX40L with a single chain fragment recognizing the tumor stroma antigen fibroblast activation protein showed a cell surface antigen-dependent increase in the activity of the ligand domain of the molecule and thus mimicked the activity of membrane OX40L upon antigen binding. Trimeric single chain OX40L fusion proteins therefore represent a novel type of OX40L-derived immunostimulatory molecule with potentially reduced systemic side effects.", "isbn" : "1742-464X (Print)$\\backslash$r1742-464X (Linking)", "pmid" : "18397322", "issn" : "1742464X", "doi" : "10.1111/j.1742-4658.2008.06382.x", "bibtexKey": "Muller2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2237a14adf2ee1432a34877f5577f848b/pumaizi", "tags" : [ "2008","olayioye","izi" ], "intraHash" : "237a14adf2ee1432a34877f5577f848b", "interHash" : "0f6812591c5a52a681df43306881038d", "label" : "Deleted in liver cancer 1 controls cell migration through a dia1-dependent signaling pathway", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Cancer Research", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18974116", "author": [ "Gerlinde Holeiter","Johanna Heering","Patrik Erlmann","Simone Schmid","Ruth Jähne","Monilola A. Olayioye" ], "authors": [ {"first" : "Gerlinde", "last" : "Holeiter"}, {"first" : "Johanna", "last" : "Heering"}, {"first" : "Patrik", "last" : "Erlmann"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Ruth", "last" : "Jähne"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "68","number": "21","pages": "8743--8751","abstract": "Deleted in liver cancer (DLC) 1 and 2 are Rho GTPase-activating proteins that are frequently down-regulated in various types of cancer. Ectopic expression in carcinoma cell lines lacking these proteins has been shown to inhibit cell migration and invasion. However, whether the loss of DLC1 or DLC2 is the cause of aberrant Rho signaling in transformed cells has not been investigated. Here, we have down-regulated DLC1 and DLC2 expression in breast cancer cells using a RNA interference approach. Silencing of DLC1 led to the stabilization of stress fibers and focal adhesions and enhanced cell motility in wound-healing as well as chemotactic Transwell assays. We provide evidence that enhanced migration of cells lacking DLC1 is dependent on the Rho effector protein Dia1 but does not require the activity of Rho kinase. By contrast, DLC2 knockdown failed to affect the migratory behavior of cells, suggesting that the two proteins have distinct functions. This is most likely due to their differential subcellular localizations, with DLC1 found in focal adhesions and DLC2 being mainly cytosolic. Collectively, our data show that DLC1 is critically involved in the control of Rho signaling and actin cytoskeleton remodeling and that its cellular loss is sufficient for the acquisition of a more migratory phenotype of breast cancer cells.", "isbn" : "4971168569301", "pmid" : "18974116", "issn" : "00085472", "doi" : "10.1158/0008-5472.CAN-08-0984", "bibtexKey": "Holeiter2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2adcdce2c362c0c29288a6ec5c7dbf9d0/pumaizi", "tags" : [ "2008","izi","kontermann" ], "intraHash" : "adcdce2c362c0c29288a6ec5c7dbf9d0", "interHash" : "d7ed36cd5c4af566e2c71abb2cf052db", "label" : "Inhibition of melanoma growth by targeting of antigen to dendritic cells via an anti-DEC-205 single-chain fragment variable molecule", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Clinical Cancer Research", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19088032", "author": [ "Theron S. Johnson","Karsten Mahnke","Volker Storn","Kurt Schönfeld","Sabine Ring","Dirk M. Nettelbeck","Hidde J. Haisma","Fabrice Le Gall","Roland E. Kontermann","Alexander H. Enk" ], "authors": [ {"first" : "Theron S.", "last" : "Johnson"}, {"first" : "Karsten", "last" : "Mahnke"}, {"first" : "Volker", "last" : "Storn"}, {"first" : "Kurt", "last" : "Schönfeld"}, {"first" : "Sabine", "last" : "Ring"}, {"first" : "Dirk M.", "last" : "Nettelbeck"}, {"first" : "Hidde J.", "last" : "Haisma"}, {"first" : "Fabrice", "last" : "Le Gall"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Alexander H.", "last" : "Enk"} ], "volume": "14","number": "24","pages": "8169--8177","abstract": "PURPOSE: Our goal was to target melanoma antigens to the dendritic cell-specific receptor DEC-205. DEC-205 is an antigen receptor expressed on dendritic cells and has been shown to guide antigens to MHC class I and II compartments for processing and presentation to T cells. EXPERIMENTAL DESIGN: The melanoma tumor-associated antigen (TAA), gp100, was fused to the single-chain fragment variable (scFv) specific for DEC-205. The binding capacity of the scFv was tested on lymph node-isolated CD11c+ cells. Mixed lymphocyte reactions were carried out to show an increased proliferative capacity of gp100 antigen-specific CD4 and CD8 T cells. Furthermore the scFv-TAA was used in a therapeutic setting using two different melanoma mouse models. RESULTS: C57Bl/6 mice were injected with scFv-DEC-205-gp100, monoclonal antibody anti-DEC-205, or PBS. Using fluorescence-activated cell sorting, we showed that lymph node CD11c+ dendritic cells stained positive for the binding of the scFv-mDEC-205-gp100 and the anti-DEC-205 monoclonal antibody, whereas the PBS-injected animals were negative. In mixed lymphocyte reactions, bone marrow-derived dendritic cells pulsed with scFv-mDEC-205-gp100 significantly increased proliferation of gp100-specific CD8+ and CD4+ T cells beyond gp100 peptide-pulsed or nonpulsed bone marrow-derived dendritic cells. Finally, in B16/F10 and RET models, a concentration-dependent suppression of tumor growth using scFv-mDEC-205-gp100 (66\\% reduction of tumor volume), in comparison with gp100 peptide vaccination, was observed. CONCLUSIONS: Our results indicate that the scFv-mDEC-205-gp100 targets TAA to dendritic cells in vivo for presentation on both MHC class I and II molecules. In vivo, this leads to an improved immune response and a decrease in tumor growth rate.", "isbn" : "4962215663", "issn" : "10780432", "doi" : "10.1158/1078-0432.CCR-08-1474", "bibtexKey": "johnson2008inhibition" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/23aaa15ddbac4ef6f038d4d98d713a560/pumaizi", "tags" : [ "2008","izi","pfizenmaier" ], "intraHash" : "3aaa15ddbac4ef6f038d4d98d713a560", "interHash" : "62efabeb0248323f039c6a1554668a24", "label" : "Single-Chain TNF, a TNF Derivative with Enhanced Stability and Antitumoral Activity", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "The Journal of Immunology", "year": "2008", "url": "http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.180.12.8176", "author": [ "A. Krippner-Heidenreich","I. Grunwald","G. Zimmermann","M. Kuhnle","J. Gerspach","T. Sterns","S. D. Shnyder","J. H. Gill","D. N. Mannel","K. Pfizenmaier","P. Scheurich" ], "authors": [ {"first" : "A.", "last" : "Krippner-Heidenreich"}, {"first" : "I.", "last" : "Grunwald"}, {"first" : "G.", "last" : "Zimmermann"}, {"first" : "M.", "last" : "Kuhnle"}, {"first" : "J.", "last" : "Gerspach"}, {"first" : "T.", "last" : "Sterns"}, {"first" : "S. D.", "last" : "Shnyder"}, {"first" : "J. H.", "last" : "Gill"}, {"first" : "D. N.", "last" : "Mannel"}, {"first" : "K.", "last" : "Pfizenmaier"}, {"first" : "P.", "last" : "Scheurich"} ], "volume": "180","number": "12","pages": "8176--8183","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.", "isbn" : "0022-1767", "pmid" : "18523283", "issn" : "0022-1767", "doi" : "10.4049/jimmunol.180.12.8176", "bibtexKey": "Krippner-Heidenreich2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2eee10ee7af4e57c8a0f8cab2dd7465a6/pumaizi", "tags" : [ "2008","izi","pfizenmaier","hausser" ], "intraHash" : "eee10ee7af4e57c8a0f8cab2dd7465a6", "interHash" : "40aa81a2816d9b99b93684ddda601b39", "label" : "Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18332134", "author": [ "Hoon Ha Chang","Weiye Wang","Sook Jhun Bong","Chelsea Wong","Angelika Hausser","Klaus Pfizenmaier","Timothy A. McKinsey","Eric N. Olson","Zheng Gen Jin" ], "authors": [ {"first" : "Hoon Ha", "last" : "Chang"}, {"first" : "Weiye", "last" : "Wang"}, {"first" : "Sook Jhun", "last" : "Bong"}, {"first" : "Chelsea", "last" : "Wong"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Timothy A.", "last" : "McKinsey"}, {"first" : "Eric N.", "last" : "Olson"}, {"first" : "Zheng Gen", "last" : "Jin"} ], "volume": "283","number": "21","pages": "14590--14599","abstract": "Vascular endothelial growth factor (VEGF) is essential for normal and pathological angiogenesis. However, the signaling pathways linked to gene regulation in VEGF-induced angiogenesis are not fully understood. Here we demonstrate a critical role of protein kinase D (PKD) and histone deacetylase 5 (HDAC5) in VEGF-induced gene expression and angiogenesis. We found that VEGF stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through a VEGF receptor 2-phospholipase Cgamma-protein kinase C-PKD-dependent pathway. We further showed that the PKD-HDAC5 pathway mediated myocyte enhancer factor-2 transcriptional activation and a specific subset of gene expression in response to VEGF, including NR4A1, an orphan nuclear receptor involved in angiogenesis. Specifically, inhibition of PKD by overexpression of the PKD kinase-negative mutant prevents VEGF-induced HDAC5 phosphorylation and nuclear export as well as NR4A1 induction. Moreover, a mutant of HDAC5 specifically deficient in PKD-dependent phosphorylation inhibited VEGF-mediated NR4A1 expression, endothelial cell migration, and in vitro angiogenesis. These findings suggest that the PKD-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis.", "isbn" : "0021-9258 (Print)$\\backslash$r0021-9258 (Linking)", "pmid" : "18332134", "issn" : "00219258", "doi" : "10.1074/jbc.M800264200", "bibtexKey": "Ha2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20c81ae7c9269836a317297be8e8bfce6/pumaizi", "tags" : [ "2008","izi","pfizenmaier","kontermann" ], "intraHash" : "0c81ae7c9269836a317297be8e8bfce6", "interHash" : "1e2131e3697ba4d9e0d4a69f0bbe3ada", "label" : "A humanized tumor necrosis factor receptor 1 (TNFR1)-specific antagonistic antibody for selective inhibition of tumor necrosis factor (TNF) action", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Immunotherapy", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18317365", "author": [ "Roland E. Kontermann","Sabine Münkel","Jens Neumeyer","Dafne Müller","Marcus Branschädel","Peter Scheurich","Klaus Pfizenmaier" ], "authors": [ {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Sabine", "last" : "Münkel"}, {"first" : "Jens", "last" : "Neumeyer"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Marcus", "last" : "Branschädel"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Klaus", "last" : "Pfizenmaier"} ], "volume": "31","number": "3","pages": "225--234","abstract": "Tumor necrosis factor (TNF) is a recognized pathogenic mediator in a number of chronic and acute inflammatory diseases. Antibodies targeting TNF have significantly improved therapy of chronic inflammatory diseases, in particular rheumatoid arthritis. Despite this success, anti-TNF treatment shows clinical efficacy only in part of the patients and is often transient, necessitating the development of alternative reagents to combat TNF action. We here describe humanization and functional properties of a TNFR1-specific, monovalent antibody fragment, designated IZI-06.1, which binds to the cysteine-rich domain 1 of TNFR1 with high affinity and competes ligand binding. IZI-06.1 serves as a receptor-selective inhibitor of proapoptotic and antiapoptotic TNF actions, revealed from complete blockage of TNFR1-dependent apoptosis and interleukin-6 induction in Kym 1 and HeLa cells, respectively, whereas TNFR2-mediated signals remained intact, evident from TNF and interleukin-2-mediated costimulation of interferon-gamma production in T cells. Accordingly, IZI-06.1 is a TNFR1-selective TNF antagonist and holds great promise to be developed into a clinically applicable therapeutic. IZI-06.1 could be a useful therapeutic alternative in all diseases already known to clinically respond to anti-TNF treatment and particularly in those diseases, where anti-TNF treatment has failed because of complete blockade of TNF action.", "isbn" : "1524-9557 (Print)\n1524-9557 (Linking)", "pmid" : "18317365", "issn" : "15249557", "doi" : "10.1097/CJI.0b013e31816a88f9", "bibtexKey": "Kontermann2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/257caab0fff537b5aa2149f3db1399cfe/pumaizi", "tags" : [ "2008","izi" ], "intraHash" : "57caab0fff537b5aa2149f3db1399cfe", "interHash" : "c037ce87a4f2e90ee3775181ef47c9f1", "label" : "Investigation of salt properties with electro-acoustic measurements and their effect on dynamic binding capacity in hydrophobic interaction chromatography", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Chromatography A", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18037423", "author": [ "Egbert Müller","Alexander Faude" ], "authors": [ {"first" : "Egbert", "last" : "Müller"}, {"first" : "Alexander", "last" : "Faude"} ], "volume": "1177","number": "2","pages": "215--225","abstract": "The pH dependence in hydrophobic interaction chromatography (HIC) is usually discussed exclusively in terms of protein dependence and there are no clear defined trends. Many of the deviations from an ideal solution are caused solely by the high salt concentration, as protein concentration is usually negligible. So pH dependency in hydrophobic interaction chromatography could also be the result of pH dependent changes of ion properties from the salt solution. The possibility that pH dependent ion hydration or ion association in highly concentrated salt solutions may influence the dynamic protein binding capacity onto HIC resins was investigated. In buffer solutions commonly used in HIC e.g. sodium chloride, ammonium sulphate and sodium citrate pH dependent maxima in the electro-acoustic signals were found. These maxima are related to an increase of the ion sizes by hydration or ion association. At low ionic strength the maxima are in the range between 4.5 and 6 and they increased in concentrated electrolyte solutions to values between 6 and 8. The range of these maxima is in the same region as dynamic protein binding capacity maxima often observed in HIC. For a qualitative interpretation of this phenomenon of increased protein stabilization by volume exclusion effect extended scaling theory can be used. This theory predicts a maximum of protein stabilization if the ratio of salt ion diameter to water is 1.8. According to the hypothesis raised here, if the pH dependent ratio of salt ion diameter to water approaches this value the transport of the protein in the pore system is less restricted and an increase in binding capacity can be produced. © 2007 Elsevier B.V. All rights reserved.", "isbn" : "0021-9673 (Print)$\\backslash$r0021-9673 (Linking)", "pmid" : "18037423", "issn" : "00219673", "doi" : "10.1016/j.chroma.2007.11.008", "bibtexKey": "Muller2008a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2263ec5de7a4e5b052142f8bb0b4488db/pumaizi", "tags" : [ "2008","izi","pfizenmaier" ], "intraHash" : "263ec5de7a4e5b052142f8bb0b4488db", "interHash" : "f909598fda9a007b7cb19ca095263bf0", "label" : "An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biotechnology","publisher":"Elsevier BV", "year": "2008", "url": "https://doi.org/10.1016%2Fj.jbiotec.2008.03.008", "author": [ "E BECKER","L FLORIN","K PFIZENMAIER","H KAUFMANN" ], "authors": [ {"first" : "E", "last" : "BECKER"}, {"first" : "L", "last" : "FLORIN"}, {"first" : "K", "last" : "PFIZENMAIER"}, {"first" : "H", "last" : "KAUFMANN"} ], "volume": "135","number": "2","pages": "217--223", "doi" : "10.1016/j.jbiotec.2008.03.008", "bibtexKey": "BECKER_2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/255cbb0199665f1431be123143815753d/pumaizi", "tags" : [ "2008","izi","kulms" ], "intraHash" : "55cbb0199665f1431be123143815753d", "interHash" : "331d90aede2bad3caf105992a129fd0b", "label" : "Identification of PP2A as a crucial regulator of the NF-$\\kappa$B feedback loop: Its inhibition by UVB turns NF-κB into a pro-apoptotic factor", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Cell Death and Differentiation", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18583989", "author": [ "S. Barisic","E. Strozyk","N. Peters","H. Walczak","D. Kulms" ], "authors": [ {"first" : "S.", "last" : "Barisic"}, {"first" : "E.", "last" : "Strozyk"}, {"first" : "N.", "last" : "Peters"}, {"first" : "H.", "last" : "Walczak"}, {"first" : "D.", "last" : "Kulms"} ], "volume": "15","number": "11","pages": "1681--1690","abstract": "Although nuclear factor-kappaB (NF-kappaB) usually exerts anti-apoptotic activity, upon activation by interleukin-1 (IL-1) it enhances ultraviolet-B radiation (UVB)-induced apoptosis. This paradoxical effect is associated with NF-kappaB-dependent pronounced secretion of tumour necrosis factor-alpha (TNF) which activates TNF-R1 in an autocrine fashion to enhance UVB-induced apoptosis. We demonstrate that sustained TNF transcription in UVB+IL-1-treated cells involves complete abrogation of the negative feedback loop of NF-kappaB preventing IkappaBalpha resynthesis, hence allowing uncontrolled NF-kappaB activity. We show that IkappaBalpha is not transcriptionally inhibited but resynthesized protein is immediately marked for degradation due to persistent inhibitor of kappaB kinasebeta (IKKbeta) activity. Continuous IKKbeta phosphorylation and activation is caused by UVB-mediated inhibition of the phosphatase PP2A. This study demonstrates that the cellular response to different NF-kappaB activators may be converted to the opposite reaction when both stimuli act in concert. Our data shed new light on the significance of negative feedback regulation of NF-kappaB and identifies PP2A as the key regulator of this process.", "isbn" : "1350-9047 (Print)", "pmid" : "18583989", "issn" : "13509047", "doi" : "10.1038/cdd.2008.98", "bibtexKey": "Barisic2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2263ec5de7a4e5b052142f8bb0b4488db/fabian", "tags" : [ "2008","izi","pfizenmaier" ], "intraHash" : "263ec5de7a4e5b052142f8bb0b4488db", "interHash" : "f909598fda9a007b7cb19ca095263bf0", "label" : "An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Journal of Biotechnology","publisher":"Elsevier BV", "year": "2008", "url": "https://doi.org/10.1016%2Fj.jbiotec.2008.03.008", "author": [ "E BECKER","L FLORIN","K PFIZENMAIER","H KAUFMANN" ], "authors": [ {"first" : "E", "last" : "BECKER"}, {"first" : "L", "last" : "FLORIN"}, {"first" : "K", "last" : "PFIZENMAIER"}, {"first" : "H", "last" : "KAUFMANN"} ], "volume": "135","number": "2","pages": "217--223", "doi" : "10.1016/j.jbiotec.2008.03.008", "bibtexKey": "BECKER_2008" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/269bbcf3fa7906c44b6eecc00d362a62e/fabian", "tags" : [ "2008","izi","mueller","kontermann" ], "intraHash" : "69bbcf3fa7906c44b6eecc00d362a62e", "interHash" : "bcd2e5cf5d41ed877a04ca196828703e", "label" : "Murine endoglin-specific single-chain Fv fragments for the analysis of vascular targeting strategies in mice", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Journal of Immunological Methods", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18790696", "author": [ "Dafne Müller","Gerhard Trunk","Anke Sichelstiel","Kirstin A. Zettlitz","Miguel Quintanilla","Roland E. Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Gerhard", "last" : "Trunk"}, {"first" : "Anke", "last" : "Sichelstiel"}, {"first" : "Kirstin A.", "last" : "Zettlitz"}, {"first" : "Miguel", "last" : "Quintanilla"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "339","number": "1","pages": "90--98","abstract": "Endoglin has been identified as a promising cell surface antigen for vascular targeting approaches in cancer therapy, e.g. employing antibody molecules as targeting moieties. However, in vivo analysis of such strategies in mouse models requires antibodies recognizing endoglin on mouse endothelial cells. Here we describe the isolation of single-chain Fv fragments (scFvs) from phage display libraries, which bind to the extracellular region of mouse endoglin. One of these clones, scFv mE12, showed strong (Kd= 11 nM) and selective binding to purified endoglin and also to the endoglin-expressing mouse endothelioma cell line eEnd.2. This antibody recognized a linear epitope located in the N-terminal region (aa 27-361) of endoglin. Cell binding was further increased by generating a bivalent scFv-Fc fusion protein composed of scFv mE12 and the human $\\gamma$1 Fc part. Moreover, scFv mE12 was endowed with an additional cysteine residue in the linker region and applied for the generation of anti-endoglin scFv immunoliposomes capable of selectively binding to endoglin-expressing cells. Thus, anti-mouse endoglin scFv mE12 should be useful to analyze vascular targeting strategies in mice. © 2008 Elsevier B.V. All rights reserved.", "isbn" : "0022-1759 (Print)$\\backslash$r0022-1759 (Linking)", "pmid" : "18790696", "issn" : "00221759", "doi" : "10.1016/j.jim.2008.08.008", "bibtexKey": "Muller2008c" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20bc51887900eea0db763789a4dbfb3d5/fabian", "tags" : [ "2008","izi","kontermann" ], "intraHash" : "0bc51887900eea0db763789a4dbfb3d5", "interHash" : "8551110d221ec17c9b29a7f85d3b481a", "label" : "Novel single-chain Fv\u2032 formats for the generation of immunoliposomes by site-directed coupling", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Bioconjugate Chemistry", "year": "2008", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17988079", "author": [ "S. K E Messerschmidt","Anke Kolbe","Dafne Müller","Michael Knoll","Jürgen Pleiss","Roland E. Kontermann" ], "authors": [ {"first" : "S. K E", "last" : "Messerschmidt"}, {"first" : "Anke", "last" : "Kolbe"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Michael", "last" : "Knoll"}, {"first" : "Jürgen", "last" : "Pleiss"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "19","number": "1","pages": "362--369","abstract": "Immunoliposomes generated by coupling of antibodies to the liposomal surface allow for an active targeting of entrapped compounds to diseased areas. Single-chain Fv fragments (scFv) represent the smallest part of an antibody containing the entire antigen-binding site. They can be coupled in a defined and site-directed manner through genetically engineered cysteine residues, for example, those added at the C-terminus. Here, we have performed a comparative analysis of various scFv' variants with cysteine residues present at the end of a C-terminal extension of varying length and composition (HC variants) or introduced in the linker sequence connecting the variable heavy and light chain domain (LC variants). Using a scFv fragment directed against fibroblast activation protein (FAP) as a model antibody, we could show that all variants can be employed for the generation of active immunoliposomes, although the presence of three additional cysteine residues in one scFv' molecule resulted in decreased binding of immunoliposomes compared to that of immunoliposomes generated with scFv' molecules containing only one additional cysteine residue. In order to further improve the scFv' format by reducing the number of additional amino acid residues, we also generated molecules with the hexahistidyl-tag incorporated into the linker sequence together with a cysteine residue either at position 1 or 3 of the linker sequence (LCH variants). These newly designed scFv' molecules may be particularly suitable for the generation of immunoliposomes and other antibody conjugates, limiting the number of additional residues in these antibody molecules to a minimum.", "isbn" : "1043-1802 (Print)$\\backslash$r1043-1802 (Linking)", "pmid" : "17988079", "issn" : "10431802", "doi" : "10.1021/bc700349k", "bibtexKey": "Messerschmidt2008" } ] }