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Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2022 Mar; Vol. 71 (3), pp. 613-625. Date of Electronic Publication: 2021 Jul 20. - Publication Year :
- 2022
-
Abstract
- Background: Natural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21.<br />Methods: K562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Purity, expansion rate, receptor expression, and functions of eNK cells were determined over four weeks of culture.<br />Results: NK cell expansion was enhanced by short exposure of soluble IL-18 and IL-21 with K562-OX40L cells. Co-culture of NK cells with K562-OX40L-mbIL-18/-21 cells resulted in remarkable expansion of NK cells from HDs (9,860-fold) and MM patients (4,929-fold) over the 28-day culture period. Moreover, eNK cells showed increased expression of major activation markers and enhanced cytotoxicity towards target K562, U266, and RPMI8226 cells.<br />Conclusions: Our data suggest that genetically engineered K562 cells expressing OX40L, mbIL-18, and mbIL-21 improve the expansion of NK cells, increase activation signals, and enhance their cytolytic activity towards MM cells.<br /> (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Subjects :
- Cells, Cultured
Coculture Techniques
Gene Expression
Humans
Immunophenotyping
Interleukin-18 genetics
Interleukins genetics
K562 Cells
Killer Cells, Natural cytology
Killer Cells, Natural metabolism
OX40 Ligand genetics
Transduction, Genetic
Transgenes
Cytotoxicity, Immunologic genetics
Interleukin-18 metabolism
Interleukins metabolism
Killer Cells, Natural immunology
Lymphocyte Activation immunology
Multiple Myeloma immunology
OX40 Ligand metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 71
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 34282497
- Full Text :
- https://doi.org/10.1007/s00262-021-02982-9