Adaptive single-KIR+NKG2C+ NK cells expanded from superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia. Adaptive single-KIR+NKG2C+ NK cells expanded from superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia

Adoptive natural killer (NK) cell therapy in combination with hematopoietic stem cell transplantation (HSCT) can provide cure for acute myeloid leukemia (AML) but is in part dependent on variable NK cell reactivity. Adaptive NK cells are a highly potent NK cell subsets that can be utilized to maximize ‘missing-self’ reactivity against tumor cells. What this study adds: It describes a novel GMP-compliant protocol to expand clinically relevant numbers of adaptive NK cells from third-party ‘superdonors’. These NK cells provide strong reactivity in a mouse model of AML as well as against primary AML blasts ex vivo. How this study might affect research, practice or policy: These pre-clinical data demonstrate the feasibility of an NK cell-based cell therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing-self recognition. Overall design: CITEseq was performed as outlined in Biolegend ‘TotalSeqTM-A Antibodies and Cell Hashing with 10x Single Cell 3' Reagent Kit v3 3.1 Protocol’ with minor modifications, using Biolegend oligo-conjugated antibodies and streptavidin TotalSeq reagents. Briefly, ADAPT-NK cells were stained with CD56-biotin mAb (Miltenyi, clone REA196), followed by TotalSeq antibodies and streptavidin-PE and Live/Dead Aqua (Invitrogen). Cells were subsequently sorted for viable CD56+ cells by flow cytometry. Submitter states: Raw data uploaded to EGA with accession EGAS00001006614<<<