Multiple Myeloma (MM) is a clonal B-cell neoplasm that affects terminally differentiated B cells (i.e. plasma cells). The disease is progressive and still incurable and is characterized by the slow proliferation of malignant plasma cells almost exclusively in the bone marrow. Disease manifestations include high levels of monoclonal Igs, immune suppression, and severe skeletal abnormalities resulting from activation of osteoclasts and bone resorption.
Our projects focus on two aspects of multiple myeloma:
- the efficient killing of the tumor cells through blockade of survival pathways and the synergistic effects of combining standard therapeutics with novel natural substances
-the re-activation of the immune system of the patients in order to facilitate effective immunotherapy.
(A) Killing of myeloma cells
In this project we want to discover new ways to induce apoptosis in the tumor cells and to stop disease progression more efficiently. Therefore we test novel substances (natural compounds in collaboration with the Institute of Pharmacological Biology/ University of Kiel) as well as inhibitors of important survival pathways of myeloma cells (AKT/PI3K, Pim-2;) for their ability to induce apoptosis in the tumor cells. We combine these substances with already utilized chemotherapeutics in order to circumvent known chemo-resistances of the tumor cells.
(B) Immunotherapy in myeloma: enhancing the competence of immune cells
Immunotherapy is a method that holds great promises in the fight against cancer. However, the efficiency of treatment is hampered by several factors amongst them the known suppression of the immune system which is seen in many patients suffering from different tumors is a major point. This is also the case in multiple myeloma: the activity of cells of the immune system is suppressed. In addition, there is a downregulation of the numbers of effective cells. Chemokines are a group of cytokines that are mainly involved in the directed migration of cells but evidence is emerging that they might play more divers roles in the progression of tumors. Some members of this protein family were found to contribute to tumor proliferation as well as to the suppression of the immune system. In our project we want to dissect the involvement of myeloma-produced chemokines in the interplay between tumor cells and cells of the immune system such as T-cells and dendritic cells. Whether and how these chemokines are supporting tumor progression and how blocking of these chemokines interferes with disease progression is a main topic in our lab. Knowledge about these interactions might be utilized in the development of more efficient immunotherapeutic strategies.
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