Abstract 3139: CD33 directed chimeric antigen receptor T cell therapy as a novel regimen prior to allogeneic stem cell transplantation in acute myeloid leukemia

Allogeneic stem cell transplantation is the only option in relapsed acute myeloid leukemia (AML). However, patients are often excluded due to refractory disease. The successful translation of Chimeric Antigen Receptor (CAR) T cell therapy to AML would constitute a vertical advance in the field. We developed a 2nd generation CAR using the anti CD33 scFv of Gemtuzumab ozogamicin, 41BB costimulation, CD3ζ signaling domain, and a lentiviral (LV) vector. In vitro, CART33 resulted in robust functions when incubated with the CD33+ cell line MOLM14. In NSGS mice (NOD SCID γc-/-(NSG), transgenic for stem cell factor, IL3 and GM-CSF) engrafted with primary AML, CART33 eradicated AML and led to a long term disease free survival (Table 1). Activity of CART33, compared to control untransduced T cellsCART33UTDP-value% Degranulation (4 hr incubation with MOLM14)98%1.3%