期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 20, 期 8, 页码 1252-1257出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2014.05.004
关键词
NK cells; Xenogeneic; Immunotherapy; Human
资金
- NIH/NCI [P01 CA65493, CA111412]
- Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201000008C, HHSN268201000007C]
- National Institutes of Health [P30 CA77598]
Natural killer (NK) cell efficacy correlates with in vivo proliferation, and we hypothesize that NK cell product manipulations may optimize this endpoint. Xenotransplantation was used to compare good manufacturing practice (GMP) grade freshly activated NK cells (FA-NK) and ex vivo expanded NK cells (Ex-NK). Cells were infused into NOD scid IL2 receptor gamma chain knockout (NSG) mice followed by IL-2, IL-15, or no cytokines. Evaluation of blood, spleen, and marrow showed that persistence and expansion was cytokine dependent, IL-15 being superior to IL-2. Cryopreservation and immediate infusion resulted in less cytotoxicity and fewer NK cells in vivo, and this could be rescued in FA-NI( by overnight culture and testing the next day. Marked differences in the kinetics and homing of FA-NK versus Ex-NK were apparent: FA-NI( cells preferentially homed to spleen and persisted longer after cytokine withdrawal. These data suggest that cryopreservation of FA-NI( and Ex-NK is detrimental and that culture conditions profoundly affect homing, persistence, and expansion of NK cells in vivo. The NSG mouse model is an adjuvant to in vitro assays before clinical testing. 2014 American Society for Blood and Marrow Transplantation.
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