Molecular Medicine

Altomonte, Jennifer

Development of oncolytic viruses as novel cancer immuno-therapeutics

The main focus of our research group centers on the engineering and use of novel recombinant, replication-competent oncolytic viral vectors, including vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV), as an immuno-therapeutic platform for cancer therapy. Our research strategies include viral engineering to enhance the tumor specificity and the immune-stimulatory potential of our therapeutic platform, as well as the development of combinatorial approaches with other immunotherapeutics, such as adoptive cell transfer and immune checkpoint blockade. The laboratory aims, not only to develop safe viral vectors that directly kill tumor cells via virus replication, but also to engineer vectors to deliver genes that may further enhance cancer killing though modulation of the tumor microenvironment and stimulation of immune responses against tumor metastases. The molecular basis for mechanisms of potential resistance to viral therapy, as well as the identification of biomarkers to predict the susceptibility of a tumor to onocolytic virus therapy, is also under investigation. We further aim to establish novel imaging modalities for noninvasively tracking viral biodistribution and replication, as well as monitoring tumor responses to viral therapy. We are a translational research lab with a strong focus on clinical development of viral therapies for tumors that are resistant to currently available therapeutics, with an emphasis on gastrointestinal tumors,such as heptocellular carcinoma and pancreatic cancer.

Selected publications:

Abdullahi S, Jäkel M, Behrend SJ, Steiger K, Topping G, Krabbe T, Colombo A, Sandig V, Schiergens TS, Thasler WE, Werner J, Lichtenthaler SF, Schmid RM, Ebert O, and Altomonte J. (2018) A novel chimeric oncolytic virus vector for improved safety and efficacy in hepatocellular carcinoma. Journal of Virology (Epub ahead of print).

Krabbe T and Altomonte J. (2018) Fusogenic viruses in oncolytic immunotherapy. Cancers, 10(7).

Altomonte J, Muñoz-Alvarez K, Shinozaki K, Baumgartner C, Kaissis G, Braren R, and Ebert O. (2016) Transarterial administration of oncolytic viruses for locoregional therapy of orthotopic HCC in rats. JoVE (110).

Marozin S, Altomonte J, Muñoz-Álvarez KA, De Toni EN, Thasler WE, Schmid RM, Ebert O. (2015) STAT3 inhibition reduces toxicity of oncolytic VSV and provides a potentially synergistic combination therapy for hepatocellular carcinoma. Cancer Gene Ther, 22(6):317-25.

Muñoz-Álvarez KA, Altomonte J, Laitinen I, Ziegler S, Steiger K, Esposito I, Schmid RM, Ebert O. (2015) PET imgaging of oncolytic VSV expressing the mutant HSV-1 thymidine kinase transgene in a preclinical HCC rat model. Mol Ther, 23(4):728-36.

Altomonte J and Ebert O. (2014) Sorting out Pandora’s box: discerning the dynamic roles of liver microenvironment in oncolytic virus therapy for hepatocellular carcinoma. Frontiers in Immunol, 4:85.

Altomonte J, Marozin S, DeToni EN, Rizzani A, Esposito I, Steiger K, Feuchtinger A, Hellerbrand C, Schmid RM, Ebert O. (2013) Antifibrotic properties of transarterial oncolytic VSV therapy for hepatocellular carcinoma in rats with thioacetamide-induced liver fibrosis. Mol Ther, 21(11):2032-42.

Marozin, S., Altomonte, J., Apfel, S., Dinh, PX., De Toni, EN., Rizzani, A., Nüssler, A., Kato, N., Schmid, RM., Pattnaik, AK., Ebert, O. (2012) Posttranslational modification of vesicular stomatitis virus glycoprotein, but not JNK inhibition, is the antiviral mechanism of SP600125. J Virol, 86(9):4844-55.