Multiple Myeloma (MM) is a hematological disorder characterized by the accumulation of neoplastic plasma cells in the bone marrow. Despite significant therapeutic advances, patients inevitably relapse due to an incomplete eradication of residual cancer cells after an effective induction therapy. Recently, it has been shown that individual myeloma cells enter a dormant state and become resistant to chemotherapy that targets dividing cells. Genes upregulated in dormant myeloma cells (e.g. Axl) were compared with proliferating cells, however no functional assays were conducted. With this proposal we aim to determine how Axl controls myeloma cell dormancy. Our general objective is to specifically target the residual cancer cells by the development of radioactively labeled nanobodies. By the use of nanobodies we are able to deliver cytotoxic radiation to cancer cells, with a minimal exposure to healthy tissue. Compared to conventional antibodies, camelid-derived nanobodies are extremely small, very stable and easy to manufacture. In addition, nanobodies will be directed against tumor-associated antigens (CS1 and Axl) that are expressed on the cancer cell surface of dormant myeloma cells to specifically target the residual cancer cells and eradicate minimal residual disease (MRD) in myeloma.
|Effective start/end date||1/10/16 → 30/09/20|
Flemish discipline codes
- Cancer therapy