Publications VP&DU

 Stability and safety key factors of the oncolytic protoparvovirus H-1 from manufacturing to human application
Veronika Frehtman, Daniel Wohlfarth, Marcus Müller, Ottheinz Krebs, Barbara Leuchs. Appl Microbiol Biotechnol. 2023 Aug;107(15):4777-4787

Upstream process optimization and micro- and macrocarrier screening for large-scale production of the oncolytic H-1 protoparvovirus
Daniel Wohlfarth 1, Veronika Frehtman 1, Marcus Müller 1, Martin Vogel 1, Linh Minh Phuc Phan 1, Adrian Brunecker 1, Barbara Leuchs 2
Appl Microbiol Biotechnol. 2021 Dec;105(24):9113-9124; doi: 10.1007/s00253-021-11642-y. Epub 2021 Nov 16.

Protocol for Efficient Generation and Characterization of Adeno-Associated Viral Vectors.
Jungmann A, Leuchs B, Rommelaere J, Katus HA, Müller OJ.
Hum Gene Ther Methods. 2017 Oct;28(5):235-246. doi: 10.1089/hgtb.2017.192. PMID:29048971

A novel scalable, robust downstream process for oncolytic rat parvovirus: isoelectric point-based elimination of empty particles.
Leuchs B, Frehtman V, Riese M, Müller M, Rommelaere J.
Appl Microbiol Biotechnol. 2017 Apr;101(8):3143-3152. doi: 10.1007/s00253-016-8071-x. Epub 2017 Jan 14.

Standardized large-scale H-1PV production process with efficient quality and quantity monitoring.
Leuchs B, Roscher M, Müller M, Kürschner K, Rommelaere J.
J Virol Methods. 2016 Mar;229:48-59. doi: 10.1016/j.jviromet.2015.11.022. Epub 2015 Dec 2.

Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.
Hajda J, Leuchs B, Angelova AL, Frehtman V, Rommelaere J, Mertens M, Pilz M, Kieser M, Krebs O, Dahm M, Huber B, Engeland CE, Mavratzas A, Hohmann N, Schreiber J, Jäger D, Halama N, Sedlaczek O, Gaida MM, Daniel V, Springfeld C, Ungerechts G.
Clin Cancer Res. 2021 Oct 15;27(20):5546-5556. doi: 10.1158/1078-0432.CCR-21-1020. Epub 2021 Aug 23. PMID: 34426438

Human Retrotransposons and the Global Shutdown of Homeostatic Innate Immunity by Oncolytic Parvovirus H-1PV in Pancreatic Cancer.
Neulinger-Muñoz M, Schaack D, Grekova SP, Bauer AS, Giese T, Salg GA, Espinet E, Leuchs B, Heller A, Nüesch JPF, Schenk M, Volkmar M, Giese NA.
Viruses. 2021 May 28;13(6):1019. doi: 10.3390/v13061019. PMID: 34071585

Fluorescence In Situ Hybridization (FISH) Detection of Viral Nucleic Acids in Oncolytic H-1 Parvovirus-Treated Human Brain Tumors.
Kiprianova I, Just A, Leuchs B, Rommelaere J, Angelova AL.
Methods Mol Biol. 2020; 2058:295-306. doi: 10.1007/978-1-4939-9794-7_20. PMID: 31486047

Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial.
Geletneky K, Hajda J, Angelova AL, Leuchs B, Capper D, Bartsch AJ, Neumann JO, Schöning T, Hüsing J, Beelte B, Kiprianova I, Roscher M, Bhat R, von Deimling A, Brück W, Just A, Frehtman V, Löbhard S, Terletskaia-Ladwig E, Fry J, Jochims K, Daniel V, Krebs O, Dahm M, Huber B, Unterberg A, Rommelaere
J. Mol Ther. 2017 Aug 24. pii: S1525-0016(17)30378-7. doi: 10.1016/j.ymthe.2017.08.016. [Epub ahead of print] PMID:28967558

A non-controlled, single arm, open label, phase II study of intravenous and intratumoral administration of ParvOryx in patients with metastatic, inoperable pancreatic cancer: ParvOryx02 protocol.
Hajda J, Lehmann M, Krebs O, Kieser M, Geletneky K, Jäger D, Dahm M, Huber B, Schöning T, Sedlaczek O, Stenzinger A, Halama N, Daniel V, Leuchs B, Angelova A, Rommelaere J, Engeland CE, Springfeld C, Ungerechts G.
BMC Cancer. 2017 Aug 29;17(1):576. doi: 10.1186/s12885-017-3604-y. PMID:28851316

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses.
Ungerechts G, Bossow S, Leuchs B, Holm PS, Rommelaere J, Coffey M, Coffin R, Bell J, Nettelbeck DM.
Mol Ther Methods Clin Dev. 2016 Apr 6;3:16018. doi: 10.1038/mtm.2016.18. eCollection 2016. Review.

Bioavailability, biodistribution, and CNS toxicity of clinical-grade parvovirus h1 after intravenous and intracerebral injection in rats.
Geletneky K, Leoni AL, Pohlmeyer-Esch G, Loebhard S, Leuchs B, Hoefer C, Jochims K, Dahm M, Huber B, Rommelaere J, Krebs O, Hajda J.
Comp Med. 2015 Feb;65(1):36-45.

Pathology, organ distribution, and immune response after single and repeated intravenous injection of rats with clinical-grade parvovirus h1.
Geletneky K, Leoni AL, Pohlmeyer-Esch G, Loebhard S, Baetz A, Leuchs B, Roscher M, Hoefer C, Jochims K, Dahm M, Huber B, Rommelaere J, Krebs O, Hajda J.
Comp Med. 2015 Feb;65(1):23-35.

Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol.
Geletneky K, Huesing J, Rommelaere J, Schlehofer JR, Leuchs B, Dahm M, Krebs O, von Knebel Doeberitz M, Huber B, Hajda J.
BMC Cancer. 2012 Mar 21;12:99. doi: 10.1186/1471-2407-12-99.

Temporal multi-omics identifies LRG1 as a vascular niche instructor of metastasis.
Singhal M, Gengenbacher N, Abdul Pari AA, Kamiyama M, Hai L, Kuhn BJ, Kallenberg DM, Kulkarni SR, Camilli C, Preuß SF, Leuchs B, Mogler C, Espinet E, Besemfelder E, Heide D, Heikenwalder M, Sprick MR, Trumpp A, Krijgsveld J, Schlesner M, Hu J, Moss SE, Greenwood J, Augustin HG.
Sci Transl Med. 2021 Sep;13(609):eabe6805. doi: 10.1126/scitranslmed.abe6805. Epub 2021 Sep 1. PMID: 34516824

SUMOylation Targets Adeno-associated Virus Capsids but Mainly Restricts Transduction by Cellular Mechanisms.
Chen Q, Njenga R, Leuchs B, Chiocca S, Kleinschmidt J, Müller M.
J Virol. 2020 Sep 15;94(19):e00871-20. doi: 10.1128/JVI.00871-20. Print 2020 Sep 15. PMID: 32669341

Various effects of AAV9-mediated βARKct gene therapy on the heart in dystrophin-deficient (mdx) mice and δ-sarcoglycan-deficient (Sgcd-/-) mice.
Bauer R, Enns H, Jungmann A, Leuchs B, Volz C, Schinkel S, Koch WJ, Raake PW, Most P, Katus HA, Müller OJ.
Neuromuscul Disord. 2019 Mar;29(3):231-241. doi: 10.1016/j.nmd.2018.12.006. Epub 2018 Dec 20. PMID: 30782477

Preclinical Testing of an Oncolytic Parvovirus in Ewing Sarcoma: Protoparvovirus H-1 Induces Apoptosis and Lytic Infection In Vitro but Fails to Improve Survival In Vivo.
Lacroix J, Kis Z, Josupeit R, Schlund F, Stroh-Dege A, Frank-Stöhr M, Leuchs B, Schlehofer JR, Rommelaere J, Dinsart C.
Viruses. 2018 Jun 3;10(6):302. doi: 10.3390/v10060302. PMID: 29865280

Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV Efficiently Induces Osteosarcoma Cell Lysis In Vitro.
Geiss C, Kis Z, Leuchs B, Frank-Stöhr M, Schlehofer JR, Rommelaere J, Dinsart C, Lacroix J.
Viruses. 2017 Oct 17;9(10). pii: E301. doi: 10.3390/v9100301. PMID:29039746

A Hepatic GAbp-AMPK Axis Links Inflammatory Signaling to Systemic Vascular Damage.
Niopek K, Üstünel BE, Seitz S, Sakurai M, Zota A, Mattijssen F, Wang X, Sijmonsma T, Feuchter Y, Gail AM, Leuchs B, Niopek D, Staufer O, Brune M, Sticht C, Gretz N, Müller-Decker K, Hammes HP, Nawroth P, Fleming T, Conkright MD, Blüher M, Zeigerer A, Herzig S, Berriel Diaz M.
Cell Rep. 2017 Aug 8;20(6):1422-1434. doi: 10.1016/j.celrep.2017.07.023. PMID:28793265

Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.
Josupeit R, Bender S, Kern S, Leuchs B, Hielscher T, Herold-Mende C, Schlehofer JR, Dinsart C, Witt O, Rommelaere J, Lacroix J.
Viruses. 2016 May 19;8(5). pii: E138. doi: 10.3390/v8050138.

Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic mice.
Gardyan A, Osen W, Zörnig I, Podola L, Agarwal M, Aulmann S, Ruggiero E, Schmidt M, Halama N, Leuchs B, von Kalle C, Beckhove P, Schneeweiss A, Jäger D, Eichmüller SB.
Int J Cancer. 2015 Jun 1;136(11):2588-97. doi: 10.1002/ijc.29322. Epub 2014 Nov 26.

Manufacturing and characterization of a recombinant adeno-associated virus type 8 reference standard material.
Ayuso E, Blouin V, Lock M, McGorray S, Leon X, Alvira MR, Auricchio A, Bucher S, Chtarto A, Clark KR, Darmon C, Doria M, Fountain W, Gao G, Gao K, Giacca M, Kleinschmidt J, Leuchs B, Melas C, Mizukami H, Müller M, Noordman Y, Bockstael O, Ozawa K, Pythoud C, Sumaroka M, Surosky R, Tenenbaum L, van der Linden I, Weins B, Wright JF, Zhang X, Zentilin L, Bosch F, Snyder RO, Moullier P.
Hum Gene Ther. 2014 Nov;25(11):977-87. doi: 10.1089/hum.2014.057.

Focal delivery of AAV2/1-transgenes into the rat brain by localized ultrasound-induced BBB Opening.
Alonso A, Reinz E, Leuchs B, Kleinschmidt J, Fatar M, Geers B, Lentacker I, Hennerici MG, de Smedt SC, Meairs S.
Ann Neurosci. 2014 Jan;21(1):22. doi: 10.5214/ans.0972.7531.210107. No abstract available.

Rapid and highly efficient inducible cardiac gene knockout in adult mice using AAV-mediated expression of Cre recombinase.
Werfel S, Jungmann A, Lehmann L, Ksienzyk J, Bekeredjian R, Kaya Z, Leuchs B, Nordheim A, Backs J, Engelhardt S, Katus HA, Müller OJ.
Cardiovasc Res. 2014 Oct 1;104(1):15-23. doi: 10.1093/cvr/cvu174. Epub 2014 Jul 31.

Oncolytic effects of parvovirus H-1 in medulloblastoma are associated with repression of master regulators of early neurogenesis. Lacroix J, Schlund F, Leuchs B, Adolph K, Sturm D, Bender S, Hielscher T, Pfister SM, Witt O, Rommelaere J, Schlehofer JR, Witt H.
Int J Cancer. 2014 Feb 1;134(3):703-16. doi: 10.1002/ijc.28386. Epub 2013 Sep 2.

Focal Delivery of AAV2/1-transgenes Into the Rat Brain by Localized Ultrasound-induced BBB Opening.
Alonso A, Reinz E, Leuchs B, Kleinschmidt J, Fatar M, Geers B, Lentacker I, Hennerici MG, de Smedt SC, Meairs S.
Mol Ther Nucleic Acids. 2013 Feb 19;2:e73. doi: 10.1038/mtna.2012.64.

TLR-9 Contributes to the Antiviral Innate Immune Sensing of Rodent Parvoviruses MVMp and H-1PV by Normal Human Immune Cells.
Raykov Z, Grekova SP, Hörlein R, Leuchs B, Giese T, Giese NA, Rommelaere J, Zawatzky R, Daeffler L.;
PLoS One. 2013;8(1):e55086. doi: 10.1371/journal.pone.0055086. Epub 2013 Jan 29.

TSC22D4 is a molecular output of hepatic wasting metabolism.
Jones A, Friedrich K, Rohm M, Schäfer M, Algire C, Kulozik P, Seibert O, Müller-Decker K, Sijmonsma T, Strzoda D, Sticht C, Gretz N, Dallinga-Thie GM, Leuchs B, Kögl M, Stremmel W, Diaz MB, Herzig S.
EMBO Mol Med. 2013 Feb;5(2):294-308. doi: 10.1002/emmm.201201869. Epub 2013 Jan 11.

Efficient recombinant parvovirus production with the help of adenovirus-derived systems.
El-Andaloussi N, Leuchs B, Bonifati S, Rommelaere J, Marchini A.
J Vis Exp. 2012 Apr 23;(62). doi:pii: 3518. 10.3791/3518.

Intranasal vaccination with AAV5 and 9 vectors against human papillomavirus type 16 in rhesus macaques.
Nieto K, Stahl-Hennig C, Leuchs B, Müller M, Gissmann L, Kleinschmidt JA.
Hum Gene Ther. 2012 Jul;23(7):733-41. doi: 10.1089/hum.2011.202. Epub 2012 Apr 18.

Retargeting of rat parvovirus H-1PV to cancer cells through genetic engineering of the viral capsid.
Allaume X, El-Andaloussi N, Leuchs B, Bonifati S, Kulkarni A, Marttila T, Kaufmann JK, Nettelbeck DM, Kleinschmidt J, Rommelaere J, Marchini A.
J Virol. 2012 Apr;86(7):3452-65. doi: 10.1128/JVI.06208-11. Epub 2012 Jan 18.

Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1.
Moehler M, Sieben M, Roth S, Springsguth F, Leuchs B, Zeidler M, Dinsart C, Rommelaere J, Galle PR.
BMC Cancer. 2011 Oct 26;11:464. doi: 10.1186/1471-2407-11-464.

Interferon γ improves the vaccination potential of oncolytic parvovirus H-1PV for the treatment of peritoneal carcinomatosis in pancreatic cancer.
Grekova SP, Aprahamian M, Daeffler L, Leuchs B, Angelova A, Giese T, Galabov A, Heller A, Giese NA, Rommelaere J, Raykov Z.
Cancer Biol Ther. 2011 Nov 15;12(10):888-95. doi: 10.4161/cbt.12.10.17678. Epub 2011 Nov 15.

Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model.
Pleger ST, Shan C, Ksienzyk J, Bekeredjian R, Boekstegers P, Hinkel R, Schinkel S, Leuchs B, Ludwig J, Qiu G, Weber C, Raake P, Koch WJ, Katus HA, Müller OJ, Most P.
Sci Transl Med. 2011 Jul 20;3(92):92ra64. doi: 10.1126/scitranslmed.3002097.

Regression of glioma in rat models by intranasal application of parvovirus h-1.
Kiprianova I, Thomas N, Ayache A, Fischer M, Leuchs B, Klein M, Rommelaere J, Schlehofer JR.
Clin Cancer Res. 2011 Aug 15;17(16):5333-42. doi: 10.1158/1078-0432.CCR-10-3124. Epub 2011 Jun 29.

Comparison of IL-10 and MCP-1-7ND gene transfer with AAV9 vectors for protection from murine autoimmune myocarditis.
Kaya Z, Leib C, Werfel S, Göser S, Öttl R, Leuchs B, Pfitzer G, Katus HA, Müller OJ.
Cardiovasc Res. 2011 Jul 1;91(1):116-23. doi: 10.1093/cvr/cvr063. Epub 2011 Feb 25.

Screening of human tumor antigens for CD4 T cell epitopes by combination of HLA-transgenic mice, recombinant adenovirus and antigen peptide libraries.
Osen W, Soltek S, Song M, Leuchs B, Steitz J, Tüting T, Eichmüller SB, Nguyen XD, Schadendorf D, Paschen A.
PLoS One. 2010 Nov 30;5(11):e14137. doi: 10.1371/journal.pone.0014137.

Novel adenovirus-based helper system to support production of recombinant parvovirus.
El-Andaloussi N, Endele M, Leuchs B, Bonifati S, Kleinschmidt J, Rommelaere J, Marchini A.
Cancer Gene Ther. 2011 Apr;18(4):240-9. doi: 10.1038/cgt.2010.73. Epub 2010 Nov 19.

Characterization of a recombinant adeno-associated virus type 2 Reference Standard Material.
Lock M, McGorray S, Auricchio A, Ayuso E, Beecham EJ, Blouin-Tavel V, Bosch F, Bose M, Byrne BJ, Caton T, Chiorini JA, Chtarto A, Clark KR, Conlon T, Darmon C, Doria M, Douar A, Flotte TR, Francis JD, Francois A, Giacca M, Korn MT, Korytov I, Leon X, Leuchs B, Lux G, Melas C, Mizukami H, Moullier P, Müller M, Ozawa K, Philipsberg T, Poulard K, Raupp C, Rivière C, Roosendaal SD, Samulski RJ, Soltys SM, Surosky R, Tenenbaum L, Thomas DL, van Montfort B, Veres G, Wright JF, Xu Y, Zelenaia O, Zentilin L, Snyder RO.
Hum Gene Ther. 2010 Oct;21(10):1273-85. doi: 10.1089/hum.2009.223.

Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library.
Ying Y, Müller OJ, Goehringer C, Leuchs B, Trepel M, Katus HA, Kleinschmidt JA.
Gene Ther. 2010 Aug;17(8):980-90. doi: 10.1038/gt.2010.44. Epub 2010 Apr 15.

Parvovirus H1 selectively induces cytotoxic effects on human neuroblastoma cells.
Lacroix J, Leuchs B, Li J, Hristov G, Deubzer HE, Kulozik AE, Rommelaere J, Schlehofer JR, Witt O.
Int J Cancer. 2010 Sep 1;127(5):1230-9. doi: 10.1002/ijc.25168.

Combined prophylactic and therapeutic intranasal vaccination against human papillomavirus type-16 using different adeno-associated virus serotype vectors.
Nieto K, Kern A, Leuchs B, Gissmann L, Müller M, Kleinschmidt JA.
Antivir Ther. 2009;14(8):1125-37. doi: 10.3851/IMP1469.

Improvement of gemcitabine-based therapy of pancreatic carcinoma by means of oncolytic parvovirus H-1PV.
Angelova AL, Aprahamian M, Grekova SP, Hajri A, Leuchs B, Giese NA, Dinsart C, Herrmann A, Balboni G, Rommelaere J, Raykov Z.
Clin Cancer Res. 2009 Jan 15;15(2):511-9. doi: 10.1158/1078-0432.CCR-08-1088.

Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein.
Sieben M, Herzer K, Zeidler M, Heinrichs V, Leuchs B, Schuler M, Cornelis JJ, Galle PR, Rommelaere J, Moehler M. World J Gastroenterol. 2008 Jun 28;14(24):3819-28.

Arming parvoviruses with CpG motifs to improve their oncosuppressive capacity.
Raykov Z, Grekova S, Leuchs B, Aprahamian M, Rommelaere J.
Int J Cancer. 2008 Jun 5 ;122(12):2880-4. doi: 10.1002/ijc.23472.

Adeno-associated virus type 2 capsids with externalized VP1/VP2 trafficking domains are generated prior to passage through the cytoplasm and are maintained until uncoating occurs in the nucleus.
Sonntag F, Bleker S, Leuchs B, Fischer R, Kleinschmidt JA.
J Virol. 2006 Nov;80(22):11040-54. Epub 2006 Sep 6.

Oncolytic murine autonomous parvovirus, a candidate vector for glioma gene therapy, is innocuous to normal and immunocompetent mouse glial cells.
Abschuetz A, Kehl T, Geibig R, Leuchs B, Rommelaere J, Régnier-Vigouroux A. Cell Tissue Res. 2006 Sep;325(3):423-36. Epub 2006 May 3.

Intranasal vaccination with recombinant adeno-associated virus type 5 against human papillomavirus type 16 L1.
Kuck D, Lau T, Leuchs B, Kern A, Müller M, Gissmann L, Kleinschmidt JA.
J Virol. 2006 Mar;80(6):2621-30.

Improved cardiac gene transfer by transcriptional and transductional targeting of adeno-associated viral vectors.
Müller OJ, Leuchs B, Pleger ST, Grimm D, Franz WM, Katus HA, Kleinschmidt JA.
Cardiovasc Res. 2006 Apr 1;70(1):70-8. Epub 2006 Jan 31.

Molecular characterization of a genetically unstable region containing the SMS critical area and a breakpoint cluster for human PNETs.
Wilgenbus KK, Seranski P, Brown A, Leuchs B, Mincheva A, Lichter P, Poustka A.
Genomics. 1997 May 15;42(1):1-10.

Barbara Leuchs is inventor / joint inventor of granted patents