Novel immunochemotherapy approaches towards improved targeting of Multiple Myeloma

Abstract

Multiple myeloma (MM) is a haematological cancer originating from antibody producing plasma cells. Clinical symptoms may include bone pain, infections, renal failure and fatigue due to anemia. MM has an important worldwide clinical impact: it accounts for 10% of all haematological disorders and 1% of all cancers. Despite several achievements in treatment modalities in the past years, MM is still considered an incurable disease. Improvement of MM therapy is a major task for investigators in the translational research field. This thesis consists of research which focuses on novel approaches by combining chemotherapy with immunotherapy. In this thesis a novel antibody daratumumab has been investigated for it’s potency to lyse MM cells as a single therapy as wel as in combination with current chemotherapies. The antibody possesses significant lysis of MM but in single use as well as combination. The combination with several chemotherapies yielded the best response in vitro as well as the implication that using the antibody on MM cells from patients who proved chemo resistant in vitro restored some of the potency of these same chemotherapies to lyse MM cells. In this thesis the potency of MM to suppress the immune system was also investigated and signalled that MM, in contact with bone marrow stroma cells, was very potent in inhibiting proliferation of immune cells and even though chemotherapy could partially but significantly restore some proliferation this inhibition could provide a major problem for future immune therapies