Translational Cancer Reaserch

Research interests:
We are mainly interested in immune regulation mechanisms in tumors and healthy tissue with a strong focus on T-cell immunology. We believe that a deeper knowledge of these processes allows the development of novel treatment strategies for cancer.
The immune system exerts potent immunosurveillance of malignant cells. However, during progression of malignant diseases these mechanisms are limited. Harnessing of the immune system for the battle against cancer has been the focus of many research efforts over the last decades. Multiple means to achieve this goal, including adoptive transfer of tumor-specific T-cells, administration of cytokines and the use of therapeutic vaccines have been tested. Indeed, many of these approaches lead to the generation of anti-tumor reacting cytotoxic T-cells, however, with limited efficacy, probably at least partially due to an immunosuppressive milieu in cancer patients.
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The manipulation of the balance between immune-stimulatory and immuno-suppressive elements might be crucial for the generation of a more effective immune response against cancer. This goal may be achieved via enhancing the anti-tumor efficacy of the involved immune cells or by turning the immuno-suppressive into a more permissive milieu, or, even better, by a combination of these approaches.
Therefore, we believe the future goal is the combination of several anti-cancer strategies, including conventional chemotherapies as well as novel immune-enhancing concepts.
Regarding our translational research profile, the aim of our efforts is to bring our experimental data and concepts into the clinic as soon as possible.

Current projects:
CD4+CD25+ regulatory T-cells (Treg) have recently been described to play a central role for maintenance of tolerance in rodents and men. Treg are actively expanded in patients suffering from several cancer types. The prognostic impact of an enlarged Treg pool has been linked to reduced survival for example in ovarian cancer. We are currently testing several strategies to circumvent Treg-induced immunosuppression in pre-clinical cancer models with a special focus on their inhibitory effects on the generation of a vaccine-induced anti-tumor immune response.
Moreover, we currently focus on the understanding and subsequent manipulation of critical “threshold regulators” in cytotoxic T-cells, with the ultimate goal to achieve a state of “induced resistance of CTL to immunosuppressive milieu effects” (exerted for example by Treg). This concept will be explored by genetic manipulation of “master-regulators” of CTL, NK cells and T-cells expressing a chimeric tumor-specific T-cell receptor before adoptive transfer for cancer therapy. This topic is currently investigated with an intimate cooperation with G. Baier (Experimental Cell Genetics Group, ...), Josef Penninger (IMBA, Vienna) and H. Rumpold (Laboratory of Molecular Biology, Dpt. Hematology/Oncology). This study should set the stage for a rapid translating the approach of “Immunaugmentation” into clinical trials using cellular products for elimination of cancer cells.

In close cooperation with Prof. C. Marth and Prof. S. Braun from the Dpt. of Obstetrics and Gynaecology we analyse the immunological microenvironment within the bone marrow compartment in patients suffering from early stage breast cacner with a special focus on the impact of the frequency of immunosuppressive T-cells (Treg) and effector T-cells (CTL, NK- and NKT-cells) with respect to the appearance of minimal residual disease.

Finally, we investigate mechanisms regulating the in vivo migratory behaviour, chemokine requirements and interactions with mast cells in a model of acute kidney failure (cooperation with Prof. Rosenkranz/Dr. K. Hochegger, Department of Nephrology).