Medical University of Vienna
Department of Medicine I
Institute for Cancer Research
Borschkegasse 8a
1090 Vienna, Austria
Phone: +43 1 40160-57577
Fax: +43 1 40160-957526
E-Mail: dietmar.herndler-brandstetter@meduniwien.ac.at
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Humanized mouse models for translational cancer research and precision medicine
Our laboratory is interested in understanding the tumor-immune microenvironment (TIME), immunotherapy resistance and tumor escape. We have developed a next-generation humanized mouse model that promotes the growth of a multitude of patient tumors and supports the development of a diverse and functional human adaptive and innate immune system. By integrating the complexity of the patient’s tumor and immune system in a novel in vivo model, we aim to advance precision immuno-oncology by providing a framework for effective combination treatment approaches for cancer patients.
Stromal regulation of immune cell development and anti-tumor immunity
Mesenchymal stromal cells maintain hematopoietic stem cells (HSC) and provide lineage-instructive differentiation signals for the development of a diverse immune system. We have developed reporter knock-in mice and conditional knock-out mice to investigate the role of distinct subsets of stromal cells for immune cell development and the regulation of immune cell responses, as seen in the tumor-stroma-immune microenvironment.
A novel humanized mouse model to investigate the tumor-immune microenvironment (TIME) and therapy resistance mechanisms
Cancer immunotherapy has provided significant clinical benefit to a number of patients with advanced disease. However, the need for more precise immunotherapies and predictive biomarkers remains of paramount importance, as complete and durable responses are only seen in 15-20% of patients. By integrating the complexity of the patient’s tumor and immune system in a novel in vivo model, we will be able to model the patient’s TIME in vivo and address whether/which checkpoint inhibitors and/or MDR-selective compounds have the potential to overcome therapy resistance mechanisms. To address this, we have developed a next-generation humanized mouse model called “MISTRG-6-15”, which supports the growth of patient-derived tumors and enables combination therapy screenings. In this research project we will (1) characterize tumor-infiltrating immune cell subsets in therapy-resistant patient cancers using single-cell sequencing and 13-color flow cytometry, (2) establish a collection of patient-derived tumor xenografts (PDX) and (3) investigate how checkpoint inhibitors and/or MDR-selective compounds remodel the TIME and affect therapy resistance and tumor escape in MISTRG-6-15 humanized mice. In summary, we will integrate the complexity of the patient’s tumor and immune system in a novel in vivo model, thereby aiming to advance precision immuno-oncology by uncovering novel therapeutic targets and prognostic markers and by providing a framework for effective combination treatment approaches for cancer patients.
Selected publications
I have chosen the IPPTO program because I have always been interested into cancer research. After finalizing my master thesis in the department of immunology, a new interest of mine aroused. Therefore, I am very pleased that I can now combine both my interests in cancer research as well as immunology through IPPTO. Aside from that, I love enjoying my free time with friends, doing some outdoor activities, enjoying nature, sun and new delicious food.