Immunogenicity of a cancerous lesion determines prognosis of the patient and the efficacy of the applied therapeutics. Whereas some viruses cause cancer, others exert anti-tumor activities and shape innate immune status in the tumor cells. We conduct studies aiming to explore both pathogenic and protective role of human endogenous viruses (HERVs) in pancreatic cancer: as cancerogenic triggers, mediators of systemic inflammation or immune modulators. The latter is of particular interest due to the recently established ability of HERVs to control endogenous production of the interferons. These cytokines represent an essential component of immunogenic cell death (ICD) – a way to die while releasing certain molecules which trigger long-term anticancer response. At the same time, interferon-dependent innate immunity is one of the major antiviral fighters.
That feature might impede efficacy of the oncolytic viruses, a new class of anticancer drugs. Over decades, we investigated therapeutic applicability of the oncotropic autonomous parvovirus H1-PV which recently entered clinical trials in the patients with brain and pancreatic cancer. In the preclinical studies, H-1PV greatly synergized with chemotherapeutic gemcitabine to boost oncolysis and to prolong survival of the tumor-bearing animals. The absolute eradication was however not achieved, in part due to the problems with the induction of an ICD. Better understanding of an interplay between HERVs, innate immunity/interferons and H-1PV in immune and tumor cells should help to optimize parvovirus-based approaches.
Most relevant publications and patents
- E Espinet, Z Gu, CD Imbusch, NA Giese, M Buscher, M Safavi, S Weisenburger, C Klein, V Vogel, M Falcone, J Insua-Rodriguez, M Reitberger, V Thiel, SO Kossi, A Muckenhuber, K Sarai, AYL Lee, E Backx, S Zarei, MM Gaida, M Rodriguez-Paredes, E Donato, HY Yen, R Eils, M Schlesner, N Pfarr, T Hackert, C Plass, B Brors, K Steiger, D Weichenhan, HE Arda, I Rooman, JL Kopp, O Strobel, W Weichert, MR Sprick and A Trumpp. Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin. Cancer Discovery, 2021. 11(3): p. 638-659.
- M Neulinger-Muñoz, D Schaack, SP Grekova, AS Bauer, T Giese, GA Salg, E Espinet, B Leuchs, A Heller, JPF Nüesch, M Schenk, M Volkmar, NA Giese. Human retrotransposons and the global shutdown of homeostatic innate immunity by oncolytic parvovirus H-1PV in pancreatic cancer. 2021 submitted.
- AL Angelova, SP Grekova, A Heller, O Kuhlmann, E Soyka, T Giese, M Aprahamian, G Bour, S Ruffer, C Cziepluch, L Daeffler, J Rommelaere, J Werner, Z Raykov and NA Giese, Complementary Induction of Immunogenic Cell Death by Oncolytic Parvovirus H-1PV and Gemcitabine in Pancreatic Cancer. J Virol, 2014. 88(10): p. 5263-76.
- AL Angelova, M Aprahamian, SP Grekova, A Hajri, B Leuchs, NA Giese, C Dinsart, A Herrmann, G Balboni, J Rommelaere and Z Raykov, Improvement of Gemcitabine-Based Therapy of Pancreatic Carcinoma by Means of Oncolytic Parvovirus H-1PV. Clinical Cancer Research, 2009. 15(2): p. 511-519.
- Z Raykov, S Grekova, L Daeffler, J Rommelaere, M Aprahamian and N Giese, Co-administration of a parvovirus and a cytokine for therapy of pancreatic cancer. Patent## 2018-01-02 CA2845637C