Associate Professor Boston University, United States
Acute myeloid leukemia (AML) begins in the blood-forming cells of the bone marrow, and has a particularly poor prognosis, with a 5-year survival rate of just over 30%. Although Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated remarkable efficacy against certain hematological malignancies, CAR T therapy for AML has been challenging due to the heterogeneity of this disease – it is characterized by a wide spectrum of mutations that influence the phenotype and disease progression for each individual patient. Therefore, in this project, we combine an OR gate logic with a split, universal, and programmable (SUPRA) CAR system that was previously developed by our lab, to target two AML-associated antigens, CD33 and FLT3, which have been identified as therapeutic targets and are currently being explored in single-target conventional CAR T clinical trials. We show that we can dose two zipFv adapters simultaneously to achieve combinatorial SUPRA targeting that eliminates target AML cell lines with varying expression levels of CD33 and FLT3.
