当前位置： SCI文献检索 > JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY期刊下所有文献 > hIL-15-gene modified human natural killer cells (NKL-IL15) exhibit anti-human leukemia functions.

hIL-15-gene modified human natural killer cells (NKL-IL15) exhibit anti-human leukemia functions.

Abstract：

PURPOSE:Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in vitro and in vivo. To further assess the applicability of NKL-IL15 cells in adoptive cellular immunotherapy for human leukemia, here we report their natural cytotoxicity against leukemia in vitro and in vivo. METHODS:Flow cytometry, ELISA and MTT methods were performed for molecular expression, cell proliferation and cytotoxicity assays. Leukemia xenograft NOD/SCID mice were established by subcutaneous injection with K562 cells, and then treated with irradiated NKL cells. RESULTS:We found NKL-IL15 cells displayed a significant high cytolysis activity against both human leukemia cell lines and primary leukemia cells from patients, accompanied with up-regulated expression of molecules related to NK cell cytotoxicity such as perforin, granzyme B and NKp80. Moreover, cytokines secreted by NKL-IL15 cells, including TNF-α and IFN-γ, could induce the expression of NKG2D ligands on target cells, which increased the susceptibility of leukemia cells to NK cell-mediated cytolysis. Encouragingly, NKL-IL15 cells significantly inhibited the growth of leukemia cells in xenografted NOD/SCID mice and prolonged the survival of tumor-bearing mice dramatically. Furthermore, NKL-IL15 cells displayed stimulatory effects on hPBMCs, indicating the immunesuppressive status of leukemia patients could be improved by NKL-IL15 cell treatment. CONCLUSIONS:These results provided evidence that IL-15 gene-modification could augment NK cell-mediated anti-human leukemia function, which would improve primary NK cell-based immunotherapy for leukemia in future.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Jiang W,Zhang C,Tian Z,Zhang J

doi

10.1007/s00432-018-2654-0

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

1279-1288

issue

7

eissn

0171-5216

issn

1432-1335

pii

10.1007/s00432-018-2654-0

journal_volume

144

pub_type

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