Alloreactive NK-cells activity to leukemia with HLA-LOH after HLA haplomismatch stem cell transplantation

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We investigated HLA expression on leukemic blasts derived from patients at diagnosis and relapse after hematopoietic stem cell transplantation (HSCT) using flow cytometry with locus-specific antibodies. HLA expression analysis was useful for analysis of donor chimerism and minimal residual diseases. We found that leukemic blasts with HLA-LOH at relapse were efficiently killed by donor NK cells. This was partially explained because ULBP2 on the leukemic blasts with HLA-LOH was highly expressed. We could monitor single KIR positive NK cells that are not inhibited by patient's HLA. Increased single KIR positive NK cells were related to higher NK cell alloreactivity. Finally, GMP grade NK cell expansion method was established using FDA approved gene modified K562 cells. These findings could establish the rationale of allogeneic NK cell therapy using KIR mismatched donor NK cells.