期刊
JOURNAL OF IMMUNOTHERAPY
卷 42, 期 2, 页码 65-72出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0000000000000250
关键词
immunotherapy; NK cells; acute myeloid leukemia; bone marrow; CD56
资金
- Production Assistance for Cellular Therapies (PACT) program from NIH/NHLBI at University of Minnesota Molecular and Cellular Therapeutics Facility (PACT) [HHSN268201000008C]
- NIH [P30CA77598, P01 CA111412, P01 CA65493]
- Children's Cancer Research Fund
- Leukemia Research Fund
- American Cancer Society
- National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000114]
Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/- denileukin diftitox, +/- low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain. The NK cell density in core biopsies showed only moderate correlation with NK cell percentage in bone marrow aspirates evaluated by flow cytometry (r(s)=0.48) suggesting that distribution of CD56(+) cells in the bone marrow niche offers unique insight into NK cell homing. Better leukemia control was associated with increased NK cell density, such that patients with <5% blasts had a higher NK cell density (P=0.01). As well, NK cell density above the median of reference group was significantly associated with morphologic remission of leukemia (P=0.01). Moreover, the NK cell density varied significantly between conditioning protocols. Our findings suggest that the use of low-dose irradiation or CD25-targeting immunocytokine (denileukin diftitox, IL2DT) as part of conditioning results in increased NK cell homing/persistence in the bone marrow. These novel results will help guide future immunotherapy with NK cells.
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