Antibodies and CARs Targeting FLT3 for the Treatment of Acute Myeloid Leukemia and Acute Lymphoid Leukemia

Fms-like tyrosine kinase 3 (FLT3) is a cytokine receptor which belongs in the receptor tyrosine kinase class III.  FLT3 is expressed on the surface of many hematopoietic progenitor cells and plays an important role in hematopoietic stem/progenitor cell survival and proliferation.  It is often overexpressed in acute lymphoblastic leukemia (ALL) and is frequently mutated in acute myeloid leukemia (AML).  The standard therapies for ALL and AML are still suboptimal for many patients, especially pediatric.  In certain types of ALL or AML, the survival rate is less than 40 and 60%, respectively.  There remains a need for effective treatments for ALL and AML.  

Inventors have discovered five high-affinity, fully human monoclonal antibodies (m1006, m1007, m1008, m1009, and m1012) targeting FLT3.  Since the antibodies are fully human, they are expected to have lower toxicity and will not require humanization or affinity maturation for clinical development.  Chimeric antigen receptor (CAR) based upon antibody-derived binding fragments of the identified antibodies were also developed.  The CAR was tested in animal models of AML and ALL and showed good efficacy against both AML and ALL in vivo. 

Competitive Advantages:

• Pediatric patients with ALL and AML have poor prognoses from the currently available treatments.  This technology represents an alternative approach to treating these patients who are unsuccessfully treated using standard chemotherapeutics.  
• Fully human antibodies expected to have lower toxicity and will not require humanization or affinity maturation for clinical development.
• Animal proof-of-concept completed.

Commercial Applications:

• Treatment of cancers that express FLT3, including ALL and AML 
• Pediatric patients with ALL and AML