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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



  • 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.

Funding

  • 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)


Head of Division

Guy Ungerechts

Prof. Dr. Dr. Guy Ungerechts
Deputy Director Medical Oncology
guy.ungerechts@nct-heidelberg.de

Phone:+49 (0)6221/42-4977
Fax:+49 (0)6221/56-7225

 



Secretary

Natalie Jäger

Natalie Jäger
natalie.jaeger@dkfz-heidelberg.de

Phone: +49 (0)6221/42-4977
Fax: +49 (0)6221/42-4809

 



Principle Investigators

Assia Angelova

Dr. Assia L. Angelova
a.angelova@dkfz.de

Phone: +49 (0)6221/42-4960
Fax: +49 (0) 6221/42-4809



Sascha Bossow

Dr. rer. nat. Sascha Bossow
sascha.bossow@med.uni-heidelberg.de

Phone: +49 (0)6221/56-34381



Christine Engeland

Univ.-Prof. Dr. med. Dr. rer. nat. Christine Engeland
christine.engeland@nct-heidelberg.de

Phone 1: +49 (0)6221/56-5454
Phone 2: +(49) (0)6221/42-4938
Fax:+49 (0)6221/56-5286



Mathias Leber

Dr. Mathias F. Leber
Mathias.Leber@nct-heidelberg.de

Phone: +49 (0)6221/56-32062



Dirk Nettelbeck

PD Dr. Dirk M. Nettelbeck
d.nettelbeck@dkfz.de

Phone: +49 (0)6221/56- 38134
Fax: +49 (0)6221/56-7225



Professor Emeritus

Jean Rommelaere

Prof. Dr. Jean Rommelaere
j.rommelaere@dkfz-heidelberg.de

Phone: +49 (0)6221/42-4960
Fax: +49 (0)6221/42-4809



Scientists

Elena Busch

Dr. med. Elena Busch
elena.busch@med.uni-heidelberg.de

Phone: +49 (0)6221/56-34643
Fax: +49 (0)6221-56-8815



Johannes Heidbüchel

Dr. rer. nat. Johannes P.W. Heidbüchel
j.heidbuechel@dkfz.de

Phone: +49 (0)6221/56-5454



Thomas Walle

Thomas Walle
t.walle@dkfz-heidelberg.de

Phone: +49 (0) 6221 56-32846



Technicians

Jessica Albert

Jessica Albert
BTA
jessica.albert@nct-heidelberg.de

Telefon 1: +49 (0)6221/56-35715 (NCT)
Telefon 2: +49 (0)6221/42-4931 (ATV)
Fax: +49 (0)6221/56-5217



Milena Barf

Milena Barf
Biologielaborantin
m.barf@dkfz.de

Telefon: +49 (0)6221/56-5454
Fax: +49 (0)6221/56-5217



Birgit Hoyler

Birgit Hoyler
MTA
birgit.hoyler@nct-heidelberg.de

Phone: +49 (0)6221/56-5454
Fax: +49 (0)6221/56-5217



Alexandra Just

Alexandra Just
MTA
a.just@dkfz.de

Phone: +49 (0)6221/56- 5454
Fax: +49 (0)6221/56-5217



Stefanie Prien

Stefanie Prien
BTA
s.prien@dkfz-heidelberg.de

Phone: +49 (0)6221/56- 5454
Fax: +49 (0)6221/56-5217



PhD and MD students



Judith Förster

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

Phone: +49 (0)6221/56- 5454
Fax: +49 (0)6221/56-5217



Lukas Kuchernig

Lukas Kuchernig
kuchernig@stud.uni-heidelberg.de

Phone: +49 (0)6221/56-5454



Gemma Pidelaserra Martí

Gemma Pidelaserra Martí, M.Sc.
g.pidelaserramarti@dkfz-heidelberg.de | gemma.pidelaserramarti@nct-heidelberg.de

Phone 1: +49 (0)6221/56-5454 (NCT)
Phone 2: +49 (0)6221/42-4931 (ATV)
Fax: +49 (0)6221/56-5217



Bachelor/Master/Medical students

Sunanjay Bajaj

Sunanjay Bajaj
Bajaj@stud.uni-heidelberg.de

Phone: +49 (0)6221/56-5454
Fax: +49 (0)6221/56-5286



Maximiliane Finkbeiner

Maximiliane Finkbeiner, B.Sc.
m.finkbeiner@dkfz-heidelberg.de

Phone 1: +49 (0)6221/56-5454 (NCT)
Phone 2: +49 (0)6221/42-4931 (ATV)
Fax: +49 (0)6221/56-5286



Katia Günther

Katia Günther, B.Sc
Katia.guenther@dkfz-heidelberg.de

Phone: +49 (0)6221-56-5454
Fax: +49 (0)6221-56-5217



Sophie Pernickel

Sophie Pernickel
boehnke@stud.uni-heidelberg.de

Phone: +49 (0)6221-56-5454



Associated Scientists

Barbara Leuchs

Barbara Leuchs, Dipl.-Ing (FH) Biotechnology
Vector Production & Development Unit (VP&DU), DKFZ
b.leuchs@dkfz-heidelberg.de

Phone: +49 (0)6221/ 42-4300
Fax: +49 (0)6221/ 42-4301





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)