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Project
Alpha-particle therapy with CS1-specific nanobodies to tackle residual cancer cells in Multiple Myeloma. (FWOKN321)
Multiple Myeloma (MM) is a hematological disorder characterized by the accumulation of neoplastic plasma cells in the bone marrow. Cancer cell dormancy is a major problem in drug resistance and relapse of myeloma patients. Despite significant therapeutic advances, relapse can occur due to the presence of residual cancer cells in the bone marrow and therefore efforts are needed to target this subpopulation of cells. The aim of our study is to specifically target the dormant cancer cells using
α-particle labeled CS1-targeting nanobodies. CS1 is a cell surface glycoprotein, overexpressed in all MM patient types (high-risk, low-risk) and highly expressed by proliferating as well as dormant, residual myeloma cells. As CS1 is not expressed by most normal issue, this antigen provides a unique target for radionuclide therapy in myeloma. Compared to conventional antibodies, camelid-derived nanobodies are extremely small, very stable and easy to manufacture. Although nanobodies were predominantly labeled with β-emitting radioisotopes for therapeutic applications, the cytotoxic effects might be improved by the use of α-emitting radionuclides. Given their short range of energy deposition, α-particles are ideal candidates to target residual cancer cells. In this proposal β- and
α-labeled CS1-specific nanobodies will be compared in their potential to eradicate minimal residual disease in myeloma
α-particle labeled CS1-targeting nanobodies. CS1 is a cell surface glycoprotein, overexpressed in all MM patient types (high-risk, low-risk) and highly expressed by proliferating as well as dormant, residual myeloma cells. As CS1 is not expressed by most normal issue, this antigen provides a unique target for radionuclide therapy in myeloma. Compared to conventional antibodies, camelid-derived nanobodies are extremely small, very stable and easy to manufacture. Although nanobodies were predominantly labeled with β-emitting radioisotopes for therapeutic applications, the cytotoxic effects might be improved by the use of α-emitting radionuclides. Given their short range of energy deposition, α-particles are ideal candidates to target residual cancer cells. In this proposal β- and
α-labeled CS1-specific nanobodies will be compared in their potential to eradicate minimal residual disease in myeloma
Date:1 Jan 2020 → 31 Dec 2020
Keywords:nanobodies, cancer cells, Multiple Myeloma, MM
Disciplines:Cancer therapy