期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 50, 期 9, 页码 1374-1385出版社
WILEY
DOI: 10.1002/eji.201948375
关键词
4-1BBL; Acute myeloid leukemia; IL-21; Minimal residual disease; NK cells
类别
资金
- National Key Research and Development Program of China [2017YFA0104500]
- National Natural Science Foundation of China [81670166, 81530046, 81870140]
- Innovative Research Groups of the National Natural Science Foundation of China [81621001]
- Beijing Municipal Science & Technology Commission [Z171100001017098]
- Project of Health Collaborative Innovation of Guangzhou City [201704020214]
- Scientific Research Foundation for Capital Medicine Development [2018-2-4084]
- Peking University Clinical Scientist Program [BMU2019LCKXJ003]
- Clinical Medicine Plus X-Young Scholars Project of Peking University [PKU2020LCXQ015]
- Peking University People's Hospital Research and Development Funds [RDX2019-14]
- Fundamental Research Funds for the Central Universities
Background Adoptive NK cell infusion is a promising immunotherapy for acute myeloid leukemia (AML) patients. The aim of this study was to test the activity of clinical-grade membrane-bound IL-21/4-1BBL-expanded NK cell products against AML in vivo. Methods Fresh peripheral blood mononuclear cells (PBMCs) were incubated with equal numbers of irradiated membrane-bound IL-21/4-1BBL-expressing K562 cells for 2-3 weeks to induce clinical-grade NK cell expansion. Results Expansion for 2 and 3 weeks produced similar to 4 and 8 x 10(9) NK cells from 2 x 10(7) PBMCs. The production of CD107a and TNF-alpha in NK cell products in response to AML cell lines and primary blasts was higher than that observed in resting NK cells. The 2-week expanded NK cell products were xenografted into immunodeficient mice with leukemia and were persistently found in the BM, spleen, liver, lung, and peripheral blood for at least 13 days; furthermore, these expanded products reduced the AML burden in vivo. Compared with matched AML patients with persistent or relapsed minimal residual disease (MRD+) who underwent regular consolidation therapy, MRD+ patients who underwent NK treatment had better overall survival and showed no major adverse events. Conclusions Clinical-grade mbIL-21/4-1BBL-expanded NK cells exhibited antileukemic activity against AML in vitro and in vivo.
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