Identification of T-cell receptors for personalised cell therapy in multiple myeloma
Modern cancer immunotherapies such as cell therapy offer unprecedented therapeutic precision and efficacy. Genetically engineered T cell receptors (TCRs) target the patient's own tumor mutations and can elicit a remarkable and durable therapeutic response in otherwise treatment-refractory solid tumors. However, T cells are highly individual and inconsistent in their function, and we currently do not understand how to identify the T cells and their TCRs that target patient-specific tumor cells in malignant hematological diseases such as multiple myeloma. For the first time, new technologies for single-cell sequencing of immune cells enable their high-throughput characterization in principle, but there is currently no method that derives a list of tumor-recognizing T cells and, as such, the TCR sequences that target the tumor to enable personalized therapy with genetically modified T cells.
The aim of this project is to use single-cell sequencing of T cells in patients with multiple myeloma to understand their diversity and function and to translate these findings into a workflow for the development of personalised T cell therapy. To this end, we are using material from patients with newly diagnosed multiple myeloma – a currently incurable malignant plasma cell disease. We will compare the T cell sequencing data from these patients with functional testing of tumour recognition. We will develop tools to identify and predict tumour-reactive T cells in order to develop patient-specific T cell therapy products. This will enable personalised cell therapy for our patients in the future. More broadly, the databases from this project should help overcome the significant challenges associated with identifying and monitoring immune cell responses to solid and non-solid tumours.
Project lead: Dr. Mirco Friedrich