Expanded clinical-grade membrane-bound IL-21/4-1BBL NK cell products exhibit activity against acute myeloid leukemia in vivo.
Eur J Immunol
; 50(9): 1374-1385, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-32357256
ABSTRACT
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 â¼4 and 8 × 109 NK cells from 2 × 107 PBMCs. The production of CD107a and TNF-α 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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Killer Cells, Natural
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Leukemia, Myeloid, Acute
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Year:
2020
Type:
Article