Priv. Doz. Dr. Uta E. Höpken, Research Group Leader
Max-Delbrück Center for Molecular Medicine (MDC)
Tel: +49 30 9406 3330
Charité - University Medicine Berlin
Lecturer / Privatdozentin
Hematological Malignancies and its Immunotherapeutic Targeting
Our group elucidates tumor-stroma interactions in hematological diseases and defines growth- and survival niches for B cell leukemia/lymphoma. By combining pre-clinical mouse models, in vivo imaging, cellular and molecular biology techniques as well as gene expression profiling substantial insight into the complex and dynamic network of tumor cells and the benign infrastructure within lymphatic tissues has been obtained. Targeting the stromal environment is an interesting therapeutic option because this benign compartment is subject to low selective pressure for genetic mutations compared with the tumor cells themselves.
Secondly, we developed Chimeric Antigen Receptor (CAR) T cells for the treatment of B cell disorders, such as a neoplastic diseases of plasma cells and mature B cells, in particular multiple myeloma (MM) or non-Hodgkin’s lymphomas (B-NHLs). Recent demonstration of disease regression of lymphoma by CD19-specific T cells has vitalized adoptive T cell therapy in the scientific community. We already succeeded to develop CAR-T cells that will allow treatment of lymphoid tumors that carry B cell differentation antigens. Examples include i) anti-tumor activity in the treatment of MM, ii) anti-plasma cell activity in dysregulated B cell responses during autoimmunity, and iii) anti-tumor activity in the treatment of mature B-NHLs.
During the next years, we aim to identify novel T cell antigens in different cancer entities and we will develop strategies to improve CAR T cell efficiency with the goal to overcome stromal barriers and the immunosuppressive microenvironment as well as exhaustion of therapeutic T cells. Additionally, we aim to visualize the kinetics of CAR T cell function in particular their killing capacities. For that we will employ two-photon and light sheet microscopy to quantify the spatiotemporal dynamics of CAR T cell-mediated killing in appropriate mouse models or in human 3-D cell culture systems.
- Gloger M, Menzel L, Grau M, Vion Anne-Clemence, Anagnostopoulos I, Zapukhlyak M, Gerlach K, Kammertöns T, Hehlgans T, Zschummel M, Lenz G, Gerhardt H, Höpken UE*, Rehm A* (2020) Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways. Cancer Research 80: 1316-1329
- Höpken UE, and Rehm A. (2019). Targeting the Tumor Microenvironment of Leukemias and Lymphomas. Trends in Cancer 5, 351-364
- Bluhm J, Kieback E, Marino, SF, Oden F, Westermann J, Chmielewski M, Abken H, Uckert W, Höpken UE*, Rehm,A* (2018). CAR T cells with enhanced sensitivity to B cell maturation antigen for the targeting of B cell non-Hodgkin’s lymphoma and multiple myeloma. Molecular Therapy 26, 1906-1919
- Gätjen M, Brand, F, Grau, M, Gerlach, K, Kettritz, R, Westermann J, Anagnostopoulos I, Lenz, P, Lenz G, Höpken UE*, Rehm, A* (2016). Splenic marginal zone granulocytes acquire an accentuated neutrophil B cell-helper phenotype in chronic lymphocytic leukemia. Cancer Research, 76: 5253-65
- Heinig K, Gätjen M, Grau, M, Stache, V, Anagnostopoulos I, Gerlach, K, Niesner R, Cseresnyes Z, Hauser A, Lenz P, Hehlgans T, Brink R, Westermann J, Dörken B, Lipp M, Lenz G, Rehm A, Höpken UE (2014). Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation. Cancer Discovery 4: 1449-1465
* equal contribution