Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies
Dirk M. Nettelbeck,
Mathias F. Leber,
Jennifer Altomonte,
Assia Angelova,
Julia Beil,
Susanne Berchtold,
Maike Delic,
Jürgen Eberle,
Anja Ehrhardt,
Christine E. Engeland,
Henry Fechner,
Karsten Geletneky,
Katrin Goepfert,
Per Sonne Holm,
Stefan Kochanek,
Florian Kreppel,
Lea Krutzke,
Florian Kühnel,
Karl Sebastian Lang,
Antonio Marchini,
Markus Moehler,
Michael D. Mühlebach,
Ulrike Naumann,
Roman Nawroth,
Jürg Nüesch,
Jean Rommelaere,
Ulrich M. Lauer,
Guy Ungerechts
Affiliations
Dirk M. Nettelbeck
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Mathias F. Leber
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Jennifer Altomonte
Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Ismaningerstr. 22, 81675 Munich, Germany
Assia Angelova
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Julia Beil
Virotherapy Center Tübingen (VCT), Department of Medical Oncology and Pneumology, Medical University Hospital, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
Susanne Berchtold
Virotherapy Center Tübingen (VCT), Department of Medical Oncology and Pneumology, Medical University Hospital, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
Maike Delic
Department of Internal Medicine, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Jürgen Eberle
Department of Dermatology, Venereology and Allergology, Skin Cancer Centre Charité, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
Anja Ehrhardt
Virology and Microbiology, Center for Biomedical Research and Education (ZBAF), Faculty of Health, Witten/Herdecke University (UW/H), Stockumer Str. 10, 58453 Witten, Germany
Christine E. Engeland
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Henry Fechner
Department of Applied Biochemistry, Institute of Biotechnology, Technical University of Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
Karsten Geletneky
Department of Neurosurgery, Klinikum Darmstadt, Grafenstraße 9, 64283 Darmstadt, Germany
Katrin Goepfert
Department of Internal Medicine, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Per Sonne Holm
Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
Stefan Kochanek
Department of Gene Therapy, Ulm University, Helmholtzstraße 8/1, 89081 Ulm, Germany
Florian Kreppel
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Research and Education (ZBAF), Faculty of Health, University Witten/Herdecke (UW/H), Stockumer Str 10, 58453 Witten, Germany
Lea Krutzke
Department of Gene Therapy, Ulm University, Helmholtzstraße 8/1, 89081 Ulm, Germany
Florian Kühnel
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School (MHH), Carl-Neuberg-Str.1, 30625 Hannover, Germany
Karl Sebastian Lang
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
Antonio Marchini
Laboratory of Oncolytic Virus Immuno-Therapeutics (LOVIT), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Markus Moehler
Department of Internal Medicine, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Michael D. Mühlebach
Division of Veterinary Medicine, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225 Langen, Germany
Ulrike Naumann
Hertie Institute for Clinical Brain Research and Center Neurology, Molecular Neurooncology, University of Tübingen, Orfried-Müller-Str. 27, 72076 Tübingen, Germany
Roman Nawroth
Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
Jürg Nüesch
Division of Virus-Associated Carcinogenesis, German Cancer Research Center, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
Jean Rommelaere
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Ulrich M. Lauer
Virotherapy Center Tübingen (VCT), Department of Medical Oncology and Pneumology, Medical University Hospital, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
Guy Ungerechts
Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.
