Malignant disease research

Development of personalized therapeutic strategies for tumor diseases in Regensburg

Personalisierte Tumortherapie
© Fraunhofer ITEM, P. Reinig

Research into metastatic disease, the development of diagnostics and pharmaceuticals is at the focus of Fraunhofer ITEM in Regensburg. The aims are to understand a patient’s individual condition, establish appropriate diagnostics, advance prevention and optimize therapies.

Special expertise

Molecular biological characterization of single cancer cells

An area of special expertise of the researchers is the molecular biological characterization of single cancer cells, which can be collected as circulating tumor cells by liquid biopsy or isolated from lymph node tissue or bone marrow as disseminated cancer cells. In order to define new treatment monitoring strategies, the liquid biopsy concept and the technology for single-cell analysis have been further developed, so that cancer cells from the cerebrospinal fluid (CSF) can now also be isolated and analyzed.

Patient-specific therapies

For the development of patient-specific therapies, for example with monoclonal antibodies as checkpoint inhibitors and advanced therapy medicinal products (ATMPs), the researchers are establishing integrated testing strategies based on ex-vivo models derived from human tumor samples. In addition, they continue to enhance the high-throughput drug screening technology based on patient-specific models. The data management established at the institute and comprehensive bioinformatics enable custom-fit analyses of the generated data.

Bioprocess development and manufacture

Bioprocess development and manufacturing of novel active molecules and investigational medicinal products for treating tumor diseases is established at Fraunhofer ITEM in Braunschweig and will be further expanded by setting up a toolbox for analysis, molecular characterization and development of production cell lines. The focus is on manufacturing processes for small bi-specific single-chain antibodies (BiTEs) that bind to T cells or CART cells and lead to tumor cells being recognized by the immune system (immunotherapy).

Risk assessment

Tumorigenesis is also an issue in the risk assessment of active pharmaceutical ingredients and chemicals. Fraunhofer ITEM is developing examples of risk assessment of nongentoxic substances by means of QSAR and in-vitro models on behalf of European regulatory authorities, including EMA, ECHA and EFSA. This will further add to the institute’s existing wealth of experience in exploring and applying integrated assessment and testing strategies (IATA) – risk assessment that is in line with the principle of the 3Rs.

Malignant disease: recent projects and highlights

 

Single-cell miRNA sequencing methods

Comparison of methods and evaluation of performance and quality using different cell lines and circulating tumor cells.

 

Investigating early metastasis

In the Collaborative Research Center / Transregio (SFB/TRR) 305, scientists investigate the mechanisms of early colony formation of tumor cells in patient-specific model systems.

 

CSF diagnostics

Based on cerebrospinal fluid (CSF) analyses, scientists want to define pre-analytical standards for biomarker studies with CSF as well as develop molecular genetic tests.

Publications

  • Mederer, T., Elsner, F., Robold, T., Grosser, C., Neu, R., Ried, M., Bleicher, S., Schamberger, T., Blochberger, I., Hofmann, H. S., Klein, C. A. (2022). EpCAM-positive disseminated cancer cells in bone marrow impact on survival of early-stage NSCLC patients. Lung Cancer 167: 73-77. doi: 10.1016/j.lungcan.2022.02.008 https://www.sciencedirect.com/science/article/pii/S0169500222003646?via%3Dihub  - Open Access
  • Metzenmacher, M., Hegedus, B., Forster, J., Schramm, A., Horn, P. A., Klein, C. A., Bielefeld, N., Ploenes, T., Aigner, C., Theegarten, D., Schildhaus, H. U., Siveke, J. T., Schuler, M., Lueong, S. S. (2022). Combined multimodal ctDNA analysis and radiological imaging for tumor surveillance in Non-small cell lung cancer. Translational Oncology 15(1): 101279. doi: 10.1016/j.tranon.2021.101279 https://www.sciencedirect.com/science/article/pii/S1936523321002709?via%3Dihub  - Open Access
  • Meumann, N., Schmithals, C., Elenschneider, L., Hansen, T., Balakrishnan, A., Hu, Q., Hook, S., Schmitz, J., Brasen, J. H., Franke, A. C., Olarewaju, O., Brandenberger, C., Talbot, S. R., Fangmann, J., Hacker, U. T., Odenthal, M., Ott, M., Piiper, A., Buning, H. (2022). Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors. Cancers 14(2). doi: 10.3390/cancers14020427 https://www.mdpi.com/2072-6694/14/2/427  - Open Access
  • Scheiter, A., Evert, K., Reibenspies, L., Cigliano, A., Annweiler, K., Muller, K., Pohmerer, L. M., Xu, H., Cui, G., Itzel, T., Materna-Reichelt, S., Coluccio, A., Honarnejad, K., Teufel, A., Brochhausen, C., Dombrowski, F., Chen, X., Evert, M., Calvisi, D. F., Utpatel, K. (2022). RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues. Molecular Oncology 16(5): 1091-1118. doi: 10.1002/1878-0261.13135 https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13135  - Open Access
  • Wege, A. K., Rom-Jurek, E. M., Jank, P., Denkert, C., Ugocsai, P., Solbach, C., Blohmer, J. U., Sinn, B., van Mackelenbergh, M., Mobus, V., Trumpp, A., Marangoni, E., Pfarr, N., Irlbeck, C., Warfsmann, J., Polzer, B., Weber, F., Ortmann, O., Loibl, S., Vladimirova, V., Brockhoff, G. (2022). mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease. International Journal of Cancer 150(8): 1357-1372. doi: 10.1002/ijc.33911 https://onlinelibrary.wiley.com/doi/10.1002/ijc.33911  - Open Access