Prof. Dr. Dr. Ungerechts

Prof. Dr. Dr. Ungerechts


Clinical Cooperation Unit Virotherapy

Head: Prof. Dr. med. Dr. rer. nat. Ungerechts

Virotherapy - Developing a unique type of cancer immunotherapy

Clinical observations of cancer remissions after viral infections laid the foundation for the field of virotherapy. Certain viruses are being explored or genetically engineered for selective replication in cancer cells, leading to tumor cell lysis. In recent years, it has become increasingly appreciated that these so-called oncolytic viruses act as a cancer immuno- (viro-) therapy via tumor vaccination effects in particular. In 2015, a first oncolytic virus was approved for the treatment of advanced melanoma in the US and Europe. Several other oncolytic viruses are currently being developed.

The CCU Virotherapy research agenda

We explore new strategies for engineering effective oncolytic viruses and combination therapies, establish processes for manufacturing oncolytic virus formulations, perform early and late phase clinical virotherapy studies and decipher mechanisms of oncolytic immunotherapy in preclinical models and patients.

Engineering oncolytic agents for maximum anti-tumor efficacy and safety

Our preclinical research program focuses on a measles vaccine virus platform with more recent projects exploring oncolytic adenoviruses and parvoviruses. Using molecular cloning, we engineer oncolytic viruses and explore combination regimens for specific medicinal purposes (see “discovery projects”). For instance, we have designed viruses to

  • direct viral infection to tumors by selective tumor cell entry or post-entry replication control (“targeting”)
  • express therapeutic proteins to implement increased potency (“arming”). Payloads include cytokines, immune checkpoint inhibitors and bispecific antibodies for alerting the patient’s immune system to the tumor (“immuno-virotherapy”)
  • establish effective combination treatments (e.g. “radio-therapy”)

Deciphering mechanisms of immuno-virotherapy

We develop and apply preclinical and patient-derived tumor models and systems immunodiagnostic tools to decipher factors both within tumor cells and the tumor microenvironment that determine oncolytic potency and anti-tumor immune activation. Our research aims at rational strategies for improving oncolytic viruses and identifying potential biomarkers of immuno-virotherapy for clinical translation (see “discovery projects” and “dissect projects”).

Advancing oncolytic viruses into clinical application

With our research, we constantly aim to identify the most effective immuno-virotherapies for clinical application. Based on our preclinical findings, we are preparing a phase I/II clinical trial with an oncolytic measles virus for immuno-virotherapy of advanced gastrointestinal cancers. To this end, we currently establish GMP-compliant virus manufacturing processes (see “develop projects”). Further completed, ongoing and upcoming trials (phases I - III) explored or explore, e.g. oncolytic parvoviruses, herpes and vaccinia viruses (“treat projects”). Importantly, the trials we initiate are accompanied by translational research programs to pinpoint mechanisms of action and identify predictive biomarker signatures of successful immuno-virotherapy (see “dissect projects”).

Overview CCU Virotherapy research agenda

  • Walle T, Bajaj S, Kraske JA, Rösner T, Cussigh CS, Kälber KA, Müller LJ, Boyoung Strobel S, Burghaus J, Kallenberger S, Stein-Thöringer C, Jenzer M, Schubert A, Kahle S, Williams A, Hoyler B, Zielske L, Skatula R, Sawall S, Leber MF, Kunes RZ, Krisam J, Fremd C, Schneeweiss A, Krauss J, Apostolidis L, Berger AK, Haag GM, Zschäbitz S, Halama N, Springfeld C, Kirsten R, Hassel JC, Jäger D, NCT ANTICIPATE Investigators & Ungerechts G. Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy. Nature Cancer, 2022
  • 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. Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma. Clin Cancer Res., 2021
  • Speck T, Heidbuechel JPW, Veinalde R, Jaeger D, von Kalle C, Ball CR, Ungerechts G, Engeland CE. Targeted BiTE expression by an oncolytic vector augments therapeutic efficacy against solid tumors. Clinical Cancer Research, 2018.

  • Veinalde R, Grossardt C, Hartmann L, Bourgeois-Daigneault MC, Bell JC, Jäger D, von Kalle C, Ungerechts G, Engeland CE. Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation. OncoImmunology, 2017.


  • Deutsche Krebshilfe (PI: G. Ungerechts)
  • HIPO (Heidelberg Center for Personalized Oncology) (PIs: G. Ungerechts and C. E. Engeland)
  • Else Kröner-Fresenius Stiftung (PI: C. E. Engeland)
  • Deutsche Forschungsgemeinschaft (PI: C. E. Engeland)
  • Wilhelm Sander-Stiftung (PI: C. E. Engeland)
  • NCT Elevator Pitch
  • Alois Hirdt-Erben und Wieland -Stiftung Heidelberg
  • Stiftung für Krebs-und Scharlachforschung
  • Else Kröner Memorial Stipendium (2019 - 2021)
  • Mildred Scheel MD Scholarship, Deutsche Krebshilfe (S. Anker, J. Dunder)
  • Charles Conrad Award 2018 (J. Heidbüchel)
  • Evangelisches Studienwerk e.V. Villigst (J. Förster)
  • Anita- und Friedrich-Reutner-Preis für Medizinische Forschung 2018 (C. E. Engeland)
  • Heidelberg School of Oncology Stipend (R. Veinalde)
  • Helmholtz International Graduate School (Fellowships to M. F. Leber, C. E. Engeland, T. Speck, J. Heidbüchel, G. Pidelaserra Martí)
  • Mildred Scheel MD Scholarship (S. Anker)
  • Boehringer Ingelheim Fonds Travel Grant (J. Heidbüchel)
  • Melanie and Eduard zur Hausen Foundation (Fellowship to R. Veinalde)
  • MD/PhD Program, Medical Faculty Heidelberg (Fellowship to C. E. Engeland)
  • Physician Scientist Program, Medical Faculty Heidelberg (Fellowships to C. E. Engeland, M. F. Leber)
  • Rahel Goitein-Straus Program, Medical Faculty Heidelberg (Fellowship to E. Czink)
  • Heinrich Behr Foundation (Fellowships to M. Singh, M. Bärtsch, K. Kubon)
  • Ontario Institute for Cancer Research (OICR) Investigator Award 2015 (G. Ungerechts)
  • Terry Fox New Investigator Award 2016 (G. Ungerechts)

The CCU Virotherapy Team 2022

Head of Division

Guy Ungerechts

Prof. Dr. Dr. Guy Ungerechts
Deputy Director Medical Oncology

Phone:+49 6221/42-4977
Fax:+49 6221/56-7225



Natalie Jäger

Natalie Jäger

Phone: +49 6221/42-4977 (ATV) / 6221/56-38134 (NCT)
Fax: +49 6221/42-4809


Principal Investigators

Assia Angelova

Dr. Assia L. Angelova

Phone: +49 6221/42-4960
Fax: +49 6221/42-4809

Sascha Bossow

Dr. rer. nat. Sascha Bossow

Phone: +49 6221/56-34381

Mathias Leber

Dr. med Dr.rer.nat Mathias F. Leber

Phone: +49 6221/56-32062

Dirk Nettelbeck

PD Dr. Dirk M. Nettelbeck

Phone: +49 6221/42-4938

Professor Emeritus

Jean Rommelaere

Prof. Dr. Jean Rommelaere

Phone: +49 6221/42-4960
Fax: +49 6221/42-4809


Elena Busch

Dr. med. Elena Busch

Phone: +49 6221/56-34643
Fax: +49 6221-56-8815

Johannes Heidbüchel

Dr. rer. nat. Johannes P.W. Heidbüchel

Phone: +49 6221/56-5454

Jonny Hertzog

Dr. rer. nat. Jonny Hertzog

Phone: +49 6221/42-4931

Thomas Walle

Dr. med. Thomas Walle

Phone: +49 6221 56-32846


Jessica Albert

Jessica Genz

Telefon 1: +49 6221/56-35715 (NCT)
Telefon 2: +49 6221/42-4931 (ATV)
Fax: +49 6221/56-5217

Milena Barf

Milena Barf

Telefon: +49 6221/56-5454
Fax: +49 6221/56-5217

Celine Bauer

Phone NCT :06221/56-35715
Phone ATV: 06221/42-4931
Fax: 06221/56-5217

Birgit Hoyler

Birgit Hoyler

Phone: +49 6221/56-5454
Fax: +49 6221/56-5217

Alexandra Just

Alexandra Just

Phone: +49 6221/56- 5454
Fax: +49 6221/56-5217

Stefanie Sawall

Stefanie Sawall

Phone 1: +49 6221/56- 5454 (NCT)
Phone 2: +49 6221/42-4931 (ATV)
Fax: +49 6221/56-5217

PhD and MD students

Martin Boos

Martin Boos, M.Sc.

Phone: +49 6221/42-4931

Katia Günther

Katia Dittus (Günther), M.Sc

Phone: +49 6221/56-5454
Fax: +49 6221/56-5217

Nicolas Duus

Nicolas Duus

Phone: +49 6221/56-5454
Fax: +49 6221/56-5217

Adrian Eilert

Phone: +49 6221/56- 5454
Fax: +49 6221/56-5217

Pierre Gommeringer

Phone 1: +49 6221 56- 5454
Phone 2: +49 6221 42- 4931

Juliane Hastedt

Juliane Hastedt

Phone: +49 6221/56- 5454
Fax: +49 6221/56-5217

Laura Kayser

Laura Kayser, M.Sc.

Phone: +49 6221/42-4931

Lukas Kuchernig

Lukas Kuchernig

Phone: +49 6221/56-5454

Levi Antonius Kuon

Phone: 06221 42-4931

Marie Szczeponik

Marie Szczeponik

Phone: +49 6221/56-5454
Fax: +49 6221/56-5217


Bachelor/Master/Medical students

Nishika Gupta, B.tech.

Phone: +49 6221 56-5454

Katja Schaudin, B.Sc.

Phone: 06221 42-4931

Associated Scientists

Barbara Leuchs

Barbara Leuchs, Dipl.-Ing (FH) Biotechnology
Vector Production & Development Unit (VP&DU), DKFZ

Phone: +49 6221/ 42-4300
Fax: +49 6221/ 42-4301


Associated Scientists:

  • Prof. Dr. med. Karim Plath, geb. Zaoui

Principal Investigator:

  • Christine E. Engeland

PhD Graduates:

  • Gemma Pidelaserra Martí
  • Gayatri Kavishwar
  • Judith M. Derani (Förster)
  • Christian Großardt
  • Mathias Leber
  • Rūta Veinalde
  • Tobias Speck
  • Johannes Heidbüchel

MD Graduates:

  • Sophie Pernickel
  • Theresa E. Schäfer
  • Marc-Andrea Bärtsch
  • Martin Singh
  • Sophie Anker

M. Sc. Graduates:

  • Annemarie Stotz
  • Sergei Dumpis
  • Clemens Olliger
  • Aurianne Pelsma
  • Katia Dittus (Günther)
  • Jan Dessila
  • Elise Jirovec   
  • Maximiliane Finkbeiner
  • Alessia Floerchinger    
  • Judith Förster
  • Laura Hartmann
  • Johannes Heidbüchel
  • Luisa Henkel
  • Lara Jeworowski
  • Mathias Leber
  • Nardine Soliman

B. Sc. Graduates:

  • Christine Ling Li Trautmann
  • Bryce Brandenstein


  • Sunanjay Bajaj
  • Joshua Hesse
  • Marie Körner
  • Clemens Olliger
  • Sergei Dumpis
  • Victoria Gilchrist
  • Linda Welte
  • Gizem Altun
  • Silja Schlue
  • Felix Schnabel
  • Saruul Jargalsaikhan
  • Jennifer Schieber
  • Julie Haenlin
  • Hannah Briesch


  • Dr. Sascha Bossow (Research Associate, 2009 – 2014)
  • Dr. Mathias Leber (Postdoc 2014 – 2018)
  • Dr. Rūta Veinalde (Postdoc 2017 – 2018)

Members of the CCU Virotherapy are involved in teaching of Oncology, Virology and Immunology for students of Medicine and Biosciences at Heidelberg University

For medical students:

-    Modul Virologie: Praktikum und POL
-    Modul Innere Medizin: POL
-    Modul Gastroenterologie: Vorlesung Gastroenterologische Onkologie
-    OSCE Vorbereitungskurs
-    Stationsunterricht

WAHLFACHTRACK Interdisziplinäre Onkologie (German)
-    Virotherapie bei Krebs: Translationale Medizin – von der Virusentwicklung zur klinischen Studie (Multimodular mit Einführung, Literaturseminar, Labor und Klinik)
-    Vorlesung Onkologische Studien
-    Seminar "Wie gestalte und präsentiere ich ein wissenschaftliches Poster?"

Betreuung von Studierenden in der Famulatur und im Praktischen Jahr
Journal Club Infection, Inflammation and Cancer
Medical dissertations

For students of Biosciences:

-    Lab rotations
-    Bachelor theses

Master Molecular Biosciences/Major Cancer Biology:
-    Lecture series “Focus in Biosciences – Module 2”, Lecture “Oncolytic Viruses”
-    Practical Course “HP-F6: Oncolytic Viruses and Gene Therapy”
-    Practical Course “HP-F12: Immunological Methods”
Master Molecular Biosciences (Majors Cancer Biology and Infectious Diseases) and Master Molecular Biotechnology:
-    Lab rotations
-    Master theses

Journal Club Infection, Inflammation and Cancer
PhD supervision/Bioscience dissertations within the international PhD program of the German Cancer Research Center (https://www.dkfz.de/en/phd-program)