Contact

 

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

Dr. Dr. Christine Engeland
christine.engeland@nct-heidelberg.de


Developing oncolytic measles virus vectors...

 

for clinical translation of immunovirotherapy.

Virotherapy

Heidelberg University Hospital
 
DKFZ
 
 
 

Significant accomplishments

Our translational research focuses on oncolytic measles viruses for cancer therapy. A Phase I/II clinical trial of immunovirotherapy for advanced gastrointestinal tumors is currently in preparation.

Achievements:

  • Proof of concept that oncolytic Measles vectors encoding bispecific T cell engagers (BiTEs) are effective against solid tumors (Speck and Heidbuechel et al., Clinical Cancer Research 2018)
  • Oncolytic Measles vectors enconding IL-12 achieve 90 % durable complete remissions in preclinical tumor models (Veinalde et al., OncoImmunology 2017)
  • Development of oncolytic Measles virus vectors encoding anti-CTLA-4 and anti-PD-L1 to enhance immunovirotherapy and reduce side effects of checkpoint blockade (Engeland et al., Molecular Therapy 2014)
  • Demonstration that oncolytic Measles virus can induce tumor-specific immunity, resulting in a protective tumor vaccination effect (Grossardt et al., Human Gene Therapy 2013)
  • Post-entry targeting of measles virus vectors via insertion of microRNA to increase safety of oncolytic agents (Leber et al. Molecular Therapy 2011; Baertsch et al., Cancer Gene Therapy 2014)
  • Establishment of targeted chemovirotherapy against lymphoma (Ungerechts et al.,Cancer Research 2007; Ungerechts et al., Gene Therapy 2010), pancreatic cancer (Bossow et al., Cancer Gene Therapy 2011), head and neck cancer (Zaoui et al., Gene Therapy 2011) and malignant melanoma (Kaufmann et al., J Invest Dermatol 2013)

Most Significant Recent Publications

  • 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 in press
  • 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 Jan 31;6(4):e1285992. doi: 10.1080/2162402X.2017.1285992.
  • 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 Nov;22(11):1949-59. doi: 10.1038/mt.2014.160.
  • Ketzer P, Kaufmann JK, Engelhardt S, Bossow S, von Kalle C, Hartig JS, Ungerechts G, Nettelbeck DM. Artificial riboswitches for gene expression and replication control of DNA and RNA viruses. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E554-62. doi: 10.1073/pnas.1318563111.
  • Grossardt C, Engeland CE, Bossow S, Halama N, Zaoui K, Leber MF, Springfeld C, Jaeger D, von Kalle C, Ungerechts G. Granulocyte-macrophage colony-stimulating factor-armed oncolytic measles virus is an effective therapeutic cancer vaccine.  Hum Gene Ther. 2013 Jul;24(7):644-54. doi: 10.1089/hum.2012.205.
  • Kaufmann JK, Bossow S, Grossardt C, Sawall S, Kupsch J, Erbs P, Hassel JC, von Kalle C, Enk AH, Nettelbeck DM, Ungerechts G. Chemovirotherapy of malignant melanoma with a targeted and armed oncolytic measles virus. J Invest Dermatol. 2013 Apr;133(4):1034-42. doi: 10.1038/jid.2012.459.
  • Leber MF, Bossow S, Leonard VH, Zaoui K, Grossardt C, Frenzke M, Miest T, Sawall S, Cattaneo R, von Kalle C, Ungerechts G. MicroRNA-sensitive oncolytic measles viruses for cancer-specific vector tropism. Mol Ther. 2011 Jun;19(6):1097-106. doi: 10.1038/mt.2011.55.

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)
  • NCT Elevator Pitch
  • Alois Hirdt-Erben und Wieland -Stiftung Heidelberg
  • Stiftung für Krebs-und Scharlachforschung

Awards and Fellowships

  • Heidelberg School of Oncology Stipend (R. Veinalde)
  • Helmholtz International Graduate School (Fellowships to M. F. Leber, C. E. Engeland, T. Speck, J. Heidbüchel)
  • 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)

Team

Prof. Dr. Dr. Guy Ungerechts, Group Leader

Dr. Dr. Christine Engeland, Head of Laboratory

Dr. Mathias Leber, Postdoc

Dr. Rūta Veinalde, Postdoc

Johannes Heidbüchel, M.Sc., PhD candidate

Judith Förster, M. Sc., PhD candidate

Kristina Kubon, MD candidate

Paul Backhaus, MD candidate

Johanna Mayer, MD candidate

Lara Jeworowski, M.Sc. candidate

Jessica Albert, Research Technician

Birgit Hoyler, Research Technician


Affiliated Physicians:

  • Dr. Elena Czink
  • Martin Singh
  • Dr. Karim Zaoui

Alumni/ Graduates:

  • PhD Graduates:
  • Christian Großardt
  • Mathias Leber
  • Christine Engeland
  • Rūta Veinalde
  • Tobias Speck

MD Graduates:

  • Marc-Andrea Bärtsch
  • Martin Singh
  • Sophie Anker

M. Sc. Graduates:

  • Mathias Leber
  • Luisa Henkel
  • Johannes Heidbüchel
  • Laura Hartmann
  • Judith Förster

B. Sc. Graduates:

  • Christine Ling Li Trautmann

Alumni:

  • Dr. Sascha Bossow (Research Associate, 2009 – 2014)