@article{OehlschlaegerMichelOsenetal.2002, author = {{\"O}hlschl{\"a}ger, Peter and Michel, Nico and Osen, Wolfram and Freyschmidt, Eva-Jasmin}, title = {T cell response to human papillomavirus 16 E7 in mice: comparison of Cr release assay, intracellular IFN-gamma production, ELISPOT and tetramer staining / Michel, Nico ; {\"O}hlschl{\"a}ger, Peter ; Osen, Wolfram ; Freyschmidt, Eva-Jasmin ; Gut{\"o}hrlein, Heidrun ;}, series = {Intervirology. 45 (2002)}, journal = {Intervirology. 45 (2002)}, isbn = {1423-0100}, pages = {290 -- 299}, year = {2002}, language = {en} } @article{OehlschlaegerOsenDelletal.2003, author = {{\"O}hlschl{\"a}ger, Peter and Osen, Wolfram and Dell, Kerstin and Faath, Stefan}, title = {Human papillomavirus type 16 L1 capsomeres induce L1-specific cytotoxic T lymphocytes and tumor regression in C57BL/6 mice / {\"O}hlschl{\"a}ger, Peter ; Osen, Wolfram ; Dell, Kerstin ; Faath, Stefan ; Garcea Robert L: ; Jochmus, Ingrid ; M{\"u}ller, Martin, Pawlita,}, series = {Journal of Virology. 77 (2003), H. 8}, journal = {Journal of Virology. 77 (2003), H. 8}, isbn = {1098-5514}, pages = {4635 -- 4645}, year = {2003}, language = {en} } @article{OehlschlaegerCorvinusOrthetal.2005, author = {{\"O}hlschl{\"a}ger, Peter and Corvinus, Florian M. and Orth, Carina and Moriggl, Richard}, title = {Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth / Corvinus, Florian, Moriggl, Richard ; Tsareva, Svetlana A. ; Wagner, Stefan ; Pfitzner, Edith B. ; Baus, Daniela ; Kaufmann, Roland : Huber, Luka}, series = {Neoplasia. 7 (2005), H. 6}, journal = {Neoplasia. 7 (2005), H. 6}, isbn = {1476-5586}, pages = {545 -- 555}, year = {2005}, language = {en} } @article{OehlschlaegerQuettingAlvarezetal.2009, author = {{\"O}hlschl{\"a}ger, Peter and Quetting, Michael and Alvarez, Gerardo and D{\"u}rst, Matthias and Gissmann, Lutz and Kaufmann, Andreas M.}, title = {Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants}, series = {International Journal of Cancer}, volume = {125}, journal = {International Journal of Cancer}, number = {1}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {189 -- 198}, year = {2009}, language = {en} } @article{OosterhuisOehlschlaegerBergetal.2011, author = {Oosterhuis, Koen and {\"O}hlschl{\"a}ger, Peter and Berg, Joost H. van den and Toebes, Mireille and Gomez, Raquel and Schumacher, Ton N. and Haanen, John B.}, title = {Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7}, series = {International Journal of Cancer}, volume = {129}, journal = {International Journal of Cancer}, number = {2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {397 -- 406}, year = {2011}, language = {en} } @article{OehlschlaegerSpiesAlvarezetal.2011, author = {{\"O}hlschl{\"a}ger, Peter and Spies, Elmar and Alvarez, Gerardo and Quetting, Michael and Groettrup, Marcus}, title = {The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA}, series = {International Journal of Cancer. 128 (2011), H. 2}, journal = {International Journal of Cancer. 128 (2011), H. 2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {473 -- 481}, year = {2011}, language = {en} } @article{LeursMezoOehlschlaegeretal.2012, author = {Leurs, Ulrike and Mezo, Gabor and {\"O}hlschl{\"a}ger, Peter and Orban, Erika and Marquard, Andrea and Manea, Marilena}, title = {Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety}, series = {Peptide Science}, volume = {98}, journal = {Peptide Science}, number = {1}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-0282}, doi = {10.1002/bip.21640}, pages = {1 -- 10}, year = {2012}, abstract = {Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.}, language = {en} } @article{ManeaLeursOrbanetal.2011, author = {Manea, Marilena and Leurs, Ulrike and Orban, Erika and Baranyai, Zsuzsa and {\"O}hlschl{\"a}ger, Peter and Marquardt, Andreas and Schulcz, Akos and Tejeda, Miguel}, title = {Enhanced Enzymatic Stability and Antitumor Activity of Daunorubicin-GnRH-III Bioconjugates Modified in Position 4}, series = {Bioconjugate Chemistry}, volume = {22}, journal = {Bioconjugate Chemistry}, number = {7}, publisher = {ACS}, address = {Washington, DC}, isbn = {1520-4812}, pages = {1320 -- 1329}, year = {2011}, language = {en} } @article{SpiessWilfriedAlvarezetal.2011, author = {Spiess, Elmar and Wilfried, Reichardt and Alvarez, Gerardo and Gottrup, Marcus and {\"O}hlschl{\"a}ger, Peter}, title = {An Artificial PAP Gene Breaks Self-tolerance and Promotes Tumor Regression in the TRAMP Model for Prostate Carcinoma}, series = {Molecular Therapy}, volume = {20}, journal = {Molecular Therapy}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {1525-0016}, pages = {555 -- 564}, year = {2011}, language = {en} } @article{OehlschlaegerOsenPeileretal.2001, author = {{\"O}hlschl{\"a}ger, Peter and Osen, Wolfram and Peiler, Tanja and Caldeira, Sandra}, title = {A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity / Osen, Wolfram ; Peiler, Tanja ; {\"O}hlschl{\"a}ger, Peter ; Caldeira, Sandra ; Faath, Stefan ; Mich}, series = {Vaccine. 19 (2001), H. 20}, journal = {Vaccine. 19 (2001), H. 20}, isbn = {0264-410X}, pages = {4276 -- 4286}, year = {2001}, language = {en} } @article{OehlschlaegerSteinbergSehretal.2005, author = {{\"O}hlschl{\"a}ger, Peter and Steinberg, Thorsten and Sehr, Peter and Osen, Wolfram}, title = {Modification of HPV 16 E7 genes: correlation between the level of protein expression and CTL response after immunization of C57BL/6 mice / Steinberg, Thorsten ; {\"O}hlschl{\"a}ger, Peter ; Sehr, Peter ; Osen, Wolfram ; Gissmann, Lutz}, series = {Vaccine. 23 (2005), H. 9}, journal = {Vaccine. 23 (2005), H. 9}, isbn = {0264-410X}, pages = {1149 -- 1157}, year = {2005}, language = {en} } @article{OehlschlaegerPesOsenetal.2006, author = {{\"O}hlschl{\"a}ger, Peter and Pes, Michaela and Osen, Wolfram and D{\"u}rst, Matthias}, title = {An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response / {\"O}hlschl{\"a}ger, Peter ; Pes, Michaela ; Osen, Wolfram ; D{\"u}rst, Matthias ; Schneider, Achim ; Gissmann, Lutz ; Kaufman}, series = {Vaccine. 24 (2006), H. 15}, journal = {Vaccine. 24 (2006), H. 15}, isbn = {0264-410X}, pages = {2880 -- 2893}, year = {2006}, language = {en} } @inproceedings{TakenagaHerreraWerneretal.2013, author = {Takenaga, Shoko and Herrera, Cony F. and Werner, Frederik and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten}, title = {Detection of the metabolic activity of cells by differential measurements based on a single light-addressable potentiometric sensor chip}, series = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, booktitle = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, organization = {Dresdner Sensor-Symposium <11, 2013>}, isbn = {978-3-9813484-5-3}, pages = {63 -- 67}, year = {2013}, language = {en} } @article{SchoeningBiselliSelmeretal.2012, author = {Sch{\"o}ning, Michael Josef and Biselli, Manfred and Selmer, Thorsten and {\"O}hlschl{\"a}ger, Peter and Baumann, Marcus and F{\"o}rster, Arnold and Poghossian, Arshak}, title = {Forschung „zwischen" den Disziplinen: das Institut f{\"u}r Nano- und Biotechnologien}, series = {Analytik news : das Online-Labormagazin f{\"u}r Labor und Analytik}, volume = {Publ. online}, journal = {Analytik news : das Online-Labormagazin f{\"u}r Labor und Analytik}, publisher = {Dr. Beyer Internet-Beratung}, address = {Ober-Ramstadt}, pages = {11 Seiten}, year = {2012}, abstract = {"Biologie trifft Mikroelektronik", das Motto des Instituts f{\"u}r Nano- und Biotechnologien (INB) an der FH Aachen, unterstreicht die zunehmende Bedeutung interdisziplin{\"a}r gepr{\"a}gter Forschungsaktivit{\"a}ten. Der thematische Zusammenschluss grundst{\"a}ndiger Disziplinen, wie die Physik, Elektrotechnik, Chemie, Biologie sowie die Materialwissenschaften, l{\"a}sst neue Forschungsgebiete entstehen, ein herausragendes Beispiel hierf{\"u}r ist die Nanotechnologie: Hier werden neue Werkstoffe und Materialien entwickelt, einzelne Nanopartikel oder Molek{\"u}le und deren Wechselwirkung untersucht oder Schichtstrukturen im Nanometerbereich aufgebaut, die neue und vorher nicht bekannte Eigenschaften hervorbringen. Vor diesem Hintergrund b{\"u}ndelt das im Jahre 2006 gegr{\"u}ndete INB die an der FH Aachen vorhandenen Kompetenzen von derzeit insgesamt sieben Laboratorien auf den Gebieten der Halbleitertechnik und Nanoelektronik, Nanostrukturen und DNA-Sensorik, der Chemo- und Biosensorik, der Enzymtechnologie, der Mikrobiologie und Pflanzenbiotechnologie, der Zellkulturtechnik, sowie der Roten Biotechnologie synergetisch. In der Nano- und Biotechnologie steckt außergew{\"o}hnliches Potenzial! Nicht zuletzt deshalb stellen sich die Forscher der Herausforderung, in diesem Bereich gemeinsam zu forschen und Schnittstellen zu nutzen, um so bei der Gestaltung neuartiger Ideen und Produkte mitzuwirken, die zuk{\"u}nftig unser allt{\"a}gliches Leben ver{\"a}ndern werden. Im Folgenden werden die verschiedenen Forschungsbereiche kurz zusammenfassend vorgestellt und vorhandene Interaktionen anhand von exemplarisch ausgew{\"a}hlten, aktuellen Forschungsprojekten skizziert.}, language = {de} } @article{TakenagaBiselliSchnitzleretal.2014, author = {Takenaga, Shoko and Biselli, Manfred and Schnitzler, Thomas and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis-Menten-like kinetics for cell culturing}, series = {Physica status solidi A : Applications and materials science}, volume = {211}, journal = {Physica status solidi A : Applications and materials science}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print)}, doi = {10.1002/pssa.201330464}, pages = {1410 -- 1415}, year = {2014}, abstract = {The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17-200 mM) follows a Michaelis-Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.}, language = {en} } @article{WhiteheadOehlschlaegerAlmajhdietal.2014, author = {Whitehead, Mark and {\"O}hlschl{\"a}ger, Peter and Almajhdi, Fahad N. and Alloza, Leonor and Marz{\´a}bal, Pablo and Meyers, Ann E. and Hitzeroth, Inga I. and Rybicki, Edward P.}, title = {Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice}, series = {BMC cancer}, journal = {BMC cancer}, number = {14:367}, publisher = {BioMed Central}, address = {London}, issn = {1471-2407}, doi = {10.1186/1471-2407-14-367}, pages = {1 -- 15}, year = {2014}, language = {en} } @article{HenkenOosterhuisOehlschlaegeretal.2012, author = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.}, title = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7}, series = {Vaccine}, volume = {30}, journal = {Vaccine}, number = {28}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0264-410X}, doi = {10.1016/j.vaccine.2012.04.013}, pages = {4259 -- 4266}, year = {2012}, abstract = {Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.}, language = {en} } @article{ImmelGruetzkeSpaeteetal.2012, author = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas}, title = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy}, series = {Chemical Communications}, volume = {48}, journal = {Chemical Communications}, number = {46}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-548X}, doi = {10.1039/C2CC31624B}, pages = {5790 -- 5792}, year = {2012}, abstract = {Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.}, language = {en} } @article{AlmajhdiSengerAmeretal.2014, author = {Almajhdi, Fahad N. and Senger, Tilo and Amer, Haitham M. and Gissmann, Lutz and {\"O}hlschl{\"a}ger, Peter}, title = {Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling)}, series = {PLOS one}, volume = {11}, journal = {PLOS one}, number = {9}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0113461}, pages = {e113461}, year = {2014}, abstract = {Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.}, language = {en} } @article{ImmelGrothHuhnetal.2011, author = {Immel, Timo A. and Groth, Ulrich and Huhn, Thomas and {\"O}hlschl{\"a}ger, Peter}, title = {Titanium salan complexes displays strong antitumor properties in vitro and in vivo in mice}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {3}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0017869}, pages = {e17869}, year = {2011}, abstract = {The anticancer activity of titanium complexes has been known since the groundbreaking studies of K{\"o}pf and K{\"o}pf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.}, language = {en} }