Prof. Dr. Dr. Ungerechts

Prof. Dr. Dr. Ungerechts

 

Clinical Cooperation Unit Virotherapy

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

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 replicate selectively 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 immunotherapy 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 investigated in clinical trials.
The CCU virotherapy focuses its preclinical research activities on a measles vaccine virus platform with further projects including oncolytic parvoviruses and adenoviruses. Our clinical research covers Phase I-III clinical trials with diverse oncolytic platforms.

Oncolytic viruses are engineered to address therapeutic needs to achieve expression of therapeutic genes („arming“), tumor-specific targeting, protection from premature clearance („stealthing“) and tumor-targeted immunomodulation. The most effective oncolytic agents are brought into clinical trials with accompanying translational research programs.

Engineering oncolytic agents for maximum safety and anti-tumor efficacy

Using reverse genetics systems and molecular cloning, oncolytic viruses can be modified for specific medicinal purposes. For instance, the  measles vaccine virus offers a versatile platform to meet therapeutic needs. In our preclinical development program, we design viruses to

  • express a therapeutic transgene to implement increased potency (“arming”). Different kinds of payloads are investigated for improved tumor cell killing or enhanced tumor-specific immune responses (“immunovirotherapy”)
  • selectively infect cancer cells via tumor-specific surface molecules (“entry targeting”)
  • block virus replication in healthy cells by exploitation of differential microRNA expression (“post-entry targeting”)
  • avoid antibody neutralization by modification of the virus surface (“stealthing”)
  • establish effective combination treatments (e.g. “radiovirotherapy”)

Deciphering mechanisms of oncolytic immunotherapy

Within the CCU Virotherapy the Research Group „Mechanisms of Oncolytic Immunotherapy“ led by Christine Engeland, MD, PhD investigates determinants of successful cancer immunotherapy using oncolytic viruses. Using preclinical and patient-derived model systems, we decipher factors both within tumor cells and the tumor microenvironment which mediate response or resistance. Our research aims at identifying rational improvement strategies and potential biomarkers for oncolytic immunotherapy for clinical translation.

Bringing oncolytic viruses into clinical application

The aim of our research is to identify the most effective oncolytic immunotherapies for clinical application. Based on our  preclinical findings, a Phase I/II clinical trial investigating oncolytic measles virus for immunovirotherapy of advanced gastrointestinal cancers is currently in preparation. Further completed, ongoing and upcoming trials (Phases I - III) explore, e.g. oncolytic parvoviruses, herpes and vaccinia viruses.
Importantly, the trials we initiate are accompanied by translational research programs to pinpoint mechanisms of action and identify predictive biomarker signatures of successful oncolytic immunotherapy.

  • 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.
  • 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. 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. BMC Cancer, 2017.
  • Engeland CE, Grossardt C, Veinalde R, Bossow S, Lutz D, Kaufmann JK, Shevchenko I, Umansky V, Nettelbeck DM, Weichert W, Jäger D, von Kalle C, Ungerechts G. CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Mol Ther, 2014.
  • 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)

Prof. Dr. Dr. Guy Ungerechts
Group Leader
guy.ungerechts@nct-heidelberg.de



Dr. Dr. Christine Engeland
Head of Research Group "Mechanisms of Oncolytic Immunotherapy"
Head of Laboratory
christine.engeland@nct-heidelberg.de



Dr. Johannes Heidbüchel
Postdoc
j.heidbuechel@dkfz-heidelberg.de



Judith Förster, M.Sc.
PhD candidate
judith.foerster@dkfz-heidelberg.de



Gemma Pidelaserra Martí, M.Sc.
PhD candidate
g.pidelaserramarti@dkfz-heidelberg.de



Kristina Kubon
MD candidate
kristina.kubon@nct-heidelberg.de



Johanna Mayer
MD candidate
johanna.mayer@nct-heidelberg.de



Jessica Dunder, M.Sc.
MD candidate



Lukas Kuchernig
MD candidate
lukas.kuchernig@nct-heidelberg.de



Živa Modic
M.Sc. candidate
z.modic@dkfz-heidelberg.de



Jessica Albert
Research Technician
jessica.albert@nct-heidelberg.de



Birgit Hoyler
Research Technician
birgit.hoyler@nct-heidelberg.de


Stefanie Prien
Research Technician
s.prien@dkfz-heidelberg.de



Affiliated Physicians

Dr. Elena Busch


Martin Singh

Dr. Karim Zaoui



Alumni/Graduates

PhD Graduates:

  • Christian Großardt
  • Mathias Leber
  • Christine Engeland
  • Rūta Veinalde
  • Tobias Speck
  • Johannes Heidbüchel

MD Graduates:

  • Marc-Andrea Bärtsch
  • Martin Singh
  • Sophie Anker

M. Sc. Graduates:

  • Mathias Leber
  • Luisa Henkel
  • Johannes Heidbüchel
  • Laura Hartmann
  • Judith Förster
  • Lara Jeworowski
  • Nardine Soliman

B. Sc. Graduates:

  • Christine Ling Li Trautmann

Alumni:

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