David Sallman, MD, Moffitt Cancer Center, Tampa, FL, discusses the preliminary findings of two clinical trials of CYAD-01, an NKG2D CAR, in relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). NKG2D is an activating receptor capable of binding 8 ligands which are overexpressed in AML/MDS. The THINK study (NCT03018405) evaluated CYAD-01 with no preconditioning and the Phase I DEPLETHINK study (NCT03466320) trialed CYAD-01 with cyclophosphamide and fludarabine preconditioning. Both used a weekly dosing schedule to enhance CAR T-cell persistence. The manufacturing process was also modified (OptimAb) from earlier trials to increase the frequency of early memory T-cells produced. The modified CYAD-01 showed significantly improved long-term anti-tumor activity compared to the original design in an in vivo model and contained a higher frequency of cells with an early memory phenotype in vitro. Data analysis is ongoing. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.