Researcher Database
Prof. Dr. Stefan Endres
Medizinische Klinik und Poliklinik IV Klinikum der Universität München
Lindwurmstraße 2a
80337 München
Program
Cancer Immunotherapy (CI)
Summary
Engineering T cells for cell-based tumor immunotherapy
We study novel approaches to engineer T cells with marker antigens for redirection of T cells using bispecific antibodies (Kobold et al. Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer. J Nat Cancer Inst 2015), with PD1-CD28 fusion proteins for protection against T cell suppression by PD-L1-expressing tumor cells (Kobold et al. Impact of a new fusion receptor on PD-1-mediated immunosuppression in adoptive T cell therapy. J Nat Cancer Inst 2015; 107) and with chemokine receptors to direct T cells into tumors (Rapp et al. C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer. Oncoimmunology 2016). We could demonstrate that CD16-based T cell activating receptors can be introduced into T cells and trigger tumor-directed T cell activation. We are currently investigating the potential of different chemokine receptors to redirect cytotoxic T cells into tumors. A second focus is on the design and validation of fusion proteins to be transduced into T cells which can be triggered by bispecific antibodies for MHC-unrestricted tumor cell lysis.
The projects are embedded in the doctorate program i-Target: Immunotargeting of Cancer (2014 bis 2022) of the Elitenetzwerk Bayern (www.immunotarget.de) and in the EU-funded Marie-Sklodowska Curie Network IMMUTRAIN (2016 bis 2020), both lead by our divison.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.