Targeted eradication of cancer stem cells by chimeric T cell receptors.

• Applicant: Dr. Patrick Schmidt
• Subject Area: Hematology, Oncology ; Immunology
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 228600964

The knowledge about the cellular composition of malignant tissue has been radically changed within the last years. It is assumed, that the initiation and maintenance of primary tumors and their corresponding metastases is mainly driven by a subpopulation of rare and therapy-resistant tumor cells. These cancer stem cells are responsible for the high number of relapses in solid as well as leukemic tumors after standard therapeutic approaches. The proven resistance against chemo- and radiotherapy of these cells urgently demands the discovery of new target structures within this subpopulation to serve as a basis for molecular therapy. The concept of adoptive immunotherapy with chimeric T cell receptors is a useful approach for concerted eradication of subgroups of cells within a tissue. The modular composition of the recombinant receptor, consisting of an antibody-based binding domain and a signalling domain from the endogenous T cell receptor complex, allows, on the one hand the manipulation of T cell signalling and on the other hand the recognition of nearly any antigen presented on the target cell. That's why it is possible to overcome the anergy of the immune system caused by the autologous tumor.The aim of this research proposal is the identification of new target structures for engineered T cells on cancer stem cells and to generate cancer stem cell specific recombinant T cell receptors. These receptors will be evaluated with respect to their effectiveness against cancer stem cells in vitro and in different spontaneous mouse models of carcinoma. This therapeutic application will generate new scientific findings regarding cancer stem cell biology, namely their influence on metastatic processes and their possible regeneration capacity.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Jörg Hülsken