Fighting cancer with organoid models, cell characteristics and zebrafish
Bavarian Center for Cancer Research (BZKF) is providing funding for three projects for targeted cancer treatment at its Erlangen location
The Erlangen location of the Bavarian Center for Cancer Research (BZKF) is providing start-up funding worth a total of 110,000 euros to three research projects at Universitätsklinikum Erlangen. The aim of the projects is to conduct fundamental research into new therapeutic approaches for treating cancer.
The research team led by Dr. Gloria Lutzny-Geier and Dr. Hannah Reimann, both at the Chair of Hematology and Oncology, have received 35,000 euros of start-up funding for their project “Characterization of the T-cell immune response in primary breast cancer organoids.” The researchers hope to discover more about the influence of chemotherapy, which is preceded by surgery to treat breast cancer, on tumor immune response. If chemotherapy has little or no effect, tumor cells can form that are resistant to therapy which the body’s immune system does not recognize and thus cannot destroy. These undetectable cancer cells can lead to the formation of metastases that significantly reduce the success rates of subsequent treatments. The research team will use a three-dimensional organoid model made of human tumor material and immune cells, or lymphocytes, that have migrated into it to investigate the interaction between tumor and immune cells. In the organoid model, the tumor material of patients remains in the composition of various cell structures where the cells can spread three dimensionally in all directions. This functions as a model of the complexity and functionality of tumors in the human body. The researchers hope to be able to analyze the effects of the mechanisms of chemotherapy on the immune response, and at the same time, identify potential markers that could indicate an increased risk of a lack of response to the therapy and could thus indicate metastasis. The aim of the project is to make a contribution to individualized therapy.
The second project funded by BZKF with a total of 35,000 euros, which is led by Prof. Dr. Felix Engel, Professorship of Experimental Kidney and Vascular Research is called “Using zebrafish to fish for therapies for cancer metastases”. The aim of the project is to improve research and develop new therapeutic approaches by studying the formation of metastases in cancer of the renal pelvis, ureter, urethra and bladder, known collectively as urothelial cell carcinoma, using zebrafish, whose disease-related genes match those of humans by between 70 and 85 percent. Urothelial cell carcinoma has only a limited response to treatments currently available. The research team is therefore transplanting marked cancer cells into transparent zebrafish larvae where metastases form after two to six days. The transparency of the larvae enables the researchers to precisely track when and where metastases form. The researchers would like to find out how to trigger ferroptosis, a recently discovered form of cell death, in order to treat metastases. They believe that the new transparent UC zebrafish model is an excellent opportunity to investigate the role of fat metabolism in the process that triggers ferroptosis.
The BZKF is providing 40,000 euros of funding to the project called “Experimental T-cell simulation using anti-tumor epitopes selected by system medicine for uveal melanoma in vitro” led by Dr. Elias A. T. Koch, Chair of Skin and Venereal Diseases. The prognosis for uveal melanoma is very poor as current treatment options are very limited. Personalized cellular treatment approaches could become the treatment of the future for this condition. These approaches are undergoing clinical trials in experimental immunotherapy at Universitätsklinikum Erlangen’s Department of Dermatology. During the last five years, an interdisciplinary team of researchers led by Prof. Dr. Julio Vera-González, Professorship of Tumor Immunology focusing on System Biology and Prof. Dr. Beatrice Schuler-Thurner at the Experimental Immune Therapy working group, have developed a highly-complex computer-assisted pipeline. It selects and evaluates tumor-specific epitopes, which are characteristics found on the surface of cancer cells. Certain cells of the immune system recognize these characteristics as intrusive and trigger other immune cells that can attack and destroy the cancer cells. The aim of the research project funded by BZKF is to test in the laboratory to what extent patient-specific tumor epitopes originating from uveal melanoma and detected by the pipeline trigger this immune response. To do so, T-cells are isolated from the blood of uveal melanoma patients, stimulated using tumor epitopes and evaluated using the latest laboratory methods. In addition, they will be compared with tumor epitopes already used in clinical trials. The researchers are hoping to find new targets on tumor cells that trigger a particularly strong reaction of the immune system towards cancer cells, enabling them to further develop experimental therapy approaches for treating uveal melanoma such as T-cell therapies.
The Bavarian Cancer Research Center (BZKF) consists of the six Bavarian university hospitals in Augsburg, Erlangen, the two sites in Munich, Regensburg and Würzburg and their associated Comprehensive Cancer Centers (CCC), which form the basis for the BKZF. The CCCs are university oncology centers that operate according to clinical structure and quality specifications.
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