Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts

Although granulocyte transfusion is a logical, therapeutic option for neutropenic patients with refractory infections, significant technical barriers have prevented its widespread use. A novel phagocyte transfusion strategy has been developed based on activation of a human myeloid cell line HL‐60. To further define the potential for HL‐60 cells to recapitulate white cell transfusions, a shortened duration of activation was evaluated, facile quality control markers were defined, and the impact of low‐dose irradiation on cell function was determined. Three days of activation resulted in increased cell viability and in vitro candidacidal capacity but with slightly higher cell replication compared with 7 days of activation. Cell viability and several flow cytometric measurements were accurate, quality control markers for HL‐60 activation. In combination with activation, low‐dose irradiation abrogated replication while sparing the candidacidal effects of the HL‐60 cells. Infusion of irradiated, activated HL‐60 cells improved survival of neutropenic, candidemic mice significantly. In summary, activated, irradiated HL‐60 cells are microbicidal, have virtually no replicative capacity, and are safe and effective at protecting neutropenic mice against an otherwise 100% fatal candidal infection. With continued development, this strategy to recapitulate neutrophil functions has the potential to serve as an effective alternative to granulocyte transfusions.