Development of innovative NANObody-based therapies to eradicate REsidual disease in Multiple Myeloma (acronym: NANOREMM)

Multiple Myeloma (MM) is the second most common hematological
cancer, characterized by clonal proliferation of plasma cells in the
bone marrow. Despite significant therapeutic advances the past
years, the majority of patients relapse due to the presence of
residual, dormant cancers cells that escape current cancer therapies.
Using an in vivo dormancy myeloma model, specific genes were
identified that potentially contribute to the induction and/or retention
of dormant myeloma cells in the bone marrow niche. With this
project, we aim to specifically target this residual cell population by
various nanobody-based strategies. Compared to conventional
antibodies, nanobodies (Nbs) are very stable, easy to manufacture
and have an excellent tissue penetration in vivo. I already developed
Nbs towards CS1 and AXL, antigens highly expressed on the
dormant cell population. The project comprises 3 specific approaches to combat myeloma cell dormancy: 1) Reactivate dormant cells by AXL-targeting Nbs in order
to improve chemosensitivity, 2) Eradicate dormant cells by radionuclide labeled CS1 Nbs (focusing on alpha therapy), 3) Develop Nb-based CART cells or NanoCARs to eliminate the dormant cell population. The proposed project promises to yield further insights in the use of nanobodies as therapeutics for MM, in order to prevent cancer recurrence by eliminating residual disease