Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.

摘要: We previously demonstrated that autologous natural killer (NK)–cell therapy after hematopoietic cell transplantation (HCT) is safe but does not provide an antitumor effect. hypothesize this due to a lack of NK-cell inhibitory receptor mismatching with tumor cells, which may be overcome by allogeneic infusions. Here, we test haploidentical, related-donor infusions in nontransplantation setting determine safety and vivo expansion. Two lower intensity outpatient immune suppressive regimens were tested: (1) lowdose cyclophosphamide methylprednisolone (2) fludarabine. A higher inpatient regimen high-dose fludarabine (HiCy/Flu) was tested patients poorprognosis acute myeloid leukemia (AML). All received subcutaneous interleukin 2 (IL-2) Patients who showed transient persistence no expansion donor cells. In contrast, the more intense Hi-Cy/Flu resulted marked rise endogenous IL-15, NK induction complete hematologic remission 5 19 poor-prognosis AML. These findings suggest haploidentical cells can persist expand have role treatment selected malignancies used alone or as adjunct HCT. (Blood. 2005;105:3051-3057)