Nanobody-based individualized AXL targeting to reverse immune suppression and overcome therapy resistance in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML), the most common form of acute leukemia in adults, is characterized by abnormal proliferation of immature myeloid cells and bone marrow failure. Despite major progress in understanding the biology of AML, treatment of elderly patients remains highly challenging and relapse often occurs. The 5year overall survival rate of adults older then 60 years is less than 10%, indicating the need for novel therapeutic approaches. Recent studies indicate that AXL, a receptor tyrosine kinase, plays a key role in various processes such as cell survival and chemoresistance of AML cells. With this project, I aim to develop AXL-specific nanobodies (Nbs) for imaging and therapeutic purposes. Nbs are camelid-derived single-domain antibody fragments, extremely small, easy to manufacture and are ideal building blocks for the generation of novel biological compounds. I will study the role of AXL in immune cells and how AXL regulates immune checkpoint expression. In addition, I will perform combination studies of AXL Nbs with chemotherapeutic agents and/or immune checkpoint inhibitors to further improve anti-tumor responses in AML. Overall, this project will expand our knowledge and improve the therapeutic potential of AXLtargeted therapies in cancer