Oncolytic viruses are a novel type of immunotherapy in cancer. The rationale of this approach is the destruction of tumor cells by viruses, which conditionally replicate in tumor cells. This immunogenic destruction of tumor cells inthe tumor microenvironment counteracts the tumor-induced immunosuppression, attracts immune cells, and eventually leads a systemic immune-stimulation, which abolished also distant metastasis. Oncolytic viruses specifically complement novel checkpoint inhibitors, as the virolysis of tumor cells provides the necessary induction T-cells, whose function is supported by the checkpoint inhibitors. In 2015, the FDA approved the first oncolytic virus. As of now oncolytic viruses prototypes have been developed for almost all virus families. The founders of Vacthera were the first to develop oncolytic influenza viruses. This was based on the fact that tumor cells have defects in the IFN or the ras pathway. In those cells the attenuated influenza virus containing deletion in the NS1 protein could effectively replicate. Moreover, tumor cells produce protease which support viral growth. The further development of oncolytic influenza viruses had been inhibited for a long time by the inability to produce stable viruses at a high titer. The new technology of Vacthera has now solved this problem enabling further development.
Publication by the founders supporting the use of influenza A virus as oncolytic viruses.
Bergmann M., I. Romirer, M. Sachet, R. Fleischhacker, A. García-Sastre, P. Palese, K, Wolff, H. Pehamberger, R. Jakesz and T. Muster. A genetically engineered influenza A virus with ras-dependent oncolytic properties. Cancer Res. 2001; 61: 8188-8193.
Muster T, Rajtarova J, Sachet M, Unger H, Fleischhacker R, Romirer I, Grassauer A, Url A, Garcia-Sastre A, Wolff K, Pehamberger H and Bergmann M. Interferon resistance promotes oncolysis by influenza virus NS1-deletion mutants. Int J Cancer 2004; 110(1):15-21
Sturlan S, Sachet M, Baumann S, Kuznetsova I, Spittler A, Bergmann M. Influenza A Virus Induces an Immediate Cytotoxic Activity in All Major Subsets of Peripheral Blood Mononuclear Cells. PLoS ONE 2009Jan 4(1); e4122
Sachet M, Friedl J, Hassler M, Ploder M, Stary G, Stift A, Bergmann M. Improvement of a dendritic cell-based tumour vaccine by an influenza virus. Eurp. J Clin Investigation 2009; 39(11): 1000-1009.
Sturlan S., Stremitzer S, Baumann S, Sachet M, Wolschek M, Egorov A, Bergmann M.
Endogenous expression of proteases in colon cancer cells facilitate influenza A viruses mediated oncolysis. Cancer Biology and Therapy 2010 Sep 2;10(6).592-596
Wolschek M, Samm E, Seper H, Sturlan S, Kuznetsova I, Schwager C, Khassidov A, Kittel C, Muster T, Egorov A, Bergmann M. Establishment of a chimeric, replication-deficient influenza A virus vector by modulation of splicing efficiency. J Virol. 2011 Mar;85(5):2469-73.
Weiss R, Sachet M, Zinngrebe J, Aschacher T, Krainer M,Hegedus B, Walczak H, Bergmann M. IL-24 sensitizes tumor cells to TLR3-mediated apoptosis, Cell Death and Differentiation, 2013 Jun;20(6):823-33.
Kuznetsova I, Shurygina A-P, Wolf B, Wolschek M, Enzmann F, Sansyzbay A Khairullin B, Sandybayev N, Stukova M , Kiselev O, Egorov A, Bergmann M. Adaptive mutation in NEP allows stable transgene expression in a chimeric influenza A virus vector. J Gen. Virol. 2014 Feb;95(Pt 2):337-49