TY - JOUR A1 - Henken, F. E. A1 - Oosterhuis, K. A1 - Öhlschläger, Peter A1 - Bosch, L. A1 - Hooijberg, E. A1 - Haanen, J. B. A. G. A1 - Steenbergen, R. D. M. T1 - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7 JF - Vaccine N2 - 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. Y1 - 2012 U6 - https://doi.org/10.1016/j.vaccine.2012.04.013 SN - 0264-410X VL - 30 IS - 28 SP - 4259 EP - 4266 PB - Elsevier CY - Amsterdam ER - TY - BOOK A1 - Lauth, Jakob A1 - Harreus, Albrecht A1 - Götz, Norbert A1 - Rang, Harald [u.a.] T1 - Preparation O-(2-Hydroxyalkyl)Oximes = of Verfahren zur Herstellung von O-(2-Hydroxy)Oximen : Europäische Patentschrift EP0775107B1 ; Veröffentlichungstag im Patentblatt: 18.11.1999 / Anmelder: BASF AG, 67063 Ludwigshafen. Erfinder: Albrecht Harreus ; Norbert Götz ; Harald Rang ... Günter Lauth Y1 - 1999 N1 - Volltext über Datenbank: http://publikationen.dpma.de/ ; Text in engl. ; Deutsche Übersetzung unter DE69512786T2 ; Internationale Veröffentlichungsnummer: WO 96/04238 PB - Europäisches Patentamt CY - [München u.a.] ER - TY - PAT A1 - Lauth, Jakob A1 - Wolf, Gerhard A1 - Burkhart, Bernd T1 - Preparation of alkoxylation products in the presence of mixed hydroxides modified with additives : United States Patent ; patent number 5,741,947 ; date of patent: Apr. 21, 1998 / assignee: BASF Aktiengesellschaft. Inventors: Gerhard Wolf ; Bernd Burkhart ; Guenter Lauth ... Y1 - 1998 N1 - Barcode: US005741947A ; Volltext über Datenbank: http://www.google.com/patents PB - [United States Trademark and Patent Office] CY - [Alexandria, VA] ER - TY - PAT A1 - Lauth, Jakob A1 - Müller, Ulrich A1 - Hoelderich, Wolfgang T1 - Preparation of aluminophosphates and silicoaluminophosphates having the AEL structure using 1,2-bis-( 4-pyridyl)-ethane : United States Patent ; patent number 5,324,493 ; date of patent: Jun. 28, 1994 / assignee: BASF Aktiengesellschaft. Inventors: Ulrich Mueller ; Wolfgang Hoelderich ; Guenter Lauth Y1 - 1994 N1 - Barcode: US005324493A ; Volltext über Datenbank: http://www.google.com/patents PB - [United States Trademark and Patent Office] CY - [Alexandria, VA] ER - TY - PAT A1 - Lauth, Jakob A1 - Dingerdissen, Uwe A1 - Henne, Andreas T1 - Preparation of amines : United States Patent ; patent number 5,817,871 ; date of patent: Oct. 6, 1998 / Assignee: BASF Aktiengesellschaft. Inventors: Uwe Dingerdissen ; Gunter Lauth ; Andreas Henne .... Y1 - 1998 N1 - Barcode: US005817871A ; Volltext über Datenbank: http://www.google.com/patents ; Falsche Namensansetzung: Gunter ... PB - [United States Trademark and Patent Office] CY - [Alexandria, VA] ER - TY - PAT A1 - Lauth, Jakob A1 - Dingerdissen, Uwe A1 - Trübenbach, Peter A1 - Steuerle, Ulrich T1 - Preparation of aziridines : United States Patent ; patent number 5,693,825 ; date of patent: Dec. 2, 1997 / assignee: BASF Aktiengesellschaft. Inventors: Uwe Dingerdissen ; Gunter Lauth ; Peter Trubenbach ; Ulrich Steuerle Y1 - 1997 N1 - Barcode: US005324493A ; Volltext über Datenbank: http://www.google.com/patents ; Falsche Namensansetzung in Datenbank: Gunter ... PB - United States Patent and Trademark Office CY - [Alexandria, VA] ER - TY - JOUR A1 - Biselli, Manfred A1 - Schmid, Georg A1 - Wandrey, Christian T1 - Preparation of cellodextrins and isolation of oligomeric side components and their characterization / Schmid, Georg ; Biselli, Manfred ; Wandrey, Christian JF - Analytical Biochemistry. 175 (1988) Y1 - 1988 SN - 0003-2697 SP - 573 EP - 583 ER - TY - PAT A1 - Lauth, Jakob A1 - Harreus, Albrecht A1 - Goetz, Norbert A1 - Rang, Harald T1 - Preparation of O-(2-hydroxyalkyl) oximes : [South African Patent ] publication number: ZA9506402 ; publication date: 1997-02-03 / applicant: BASF AG. Inventor: Harreus, Albrecht ; Goetz, Norbert ; Rang, Harald .... Lauth, Guenter ... Y1 - 1997 N1 - Also published as WO9604238 PB - [South African Companies and Intellectual Property Registration Office] CY - [Pretoria] ER - TY - PAT A1 - Lauth, Jakob T1 - Preparation of O-(2-hydroxyalkyl) oximes : patent application CA 2196452 ; filing date: 1995-07-28 ; national entry: 1997-01-30 / applicants: BASF Aktiengesellschaft. Inventors: Harreus, Albrecht ; Gotz, Norbert ; Rang, Harald ... Lauth, Guenther ... Y1 - 1995 N1 - International publication number: WO1996/004238 PB - Canadian International Property Office CY - [Gatineau, Quebec] ER - TY - JOUR A1 - Kotter, Michael A1 - Hammon, U. T1 - Preparation of pellets with well-defined pore structure / U. Hammon ; A. Kotter JF - International chemical engineering. 26 (1986), H. 4 Y1 - 1986 SN - 0020-6318 SP - 563 EP - 573 ER -