Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy
Immune Network
; : e31-2018.
Article
in En
| WPRIM
| ID: wpr-716248
Responsible library:
WPRO
ABSTRACT
Allogeneic natural killer (NK) cell therapy is a potential therapeutic approach for a variety of solid tumors. We established an expansion method for large-scale production of highly purified and functionally active NK cells, as well as a freezing medium for the expanded NK cells. In the present study, we assessed the effect of cryopreservation on the expanded NK cells in regards to viability, phenotype, and anti-tumor activity. NK cells were enormously expanded (about 15,000-fold expansion) with high viability and purity by stimulating CD³⁺ T cell-depleted peripheral blood mononuclear cells (PBMCs) with irradiated autologous PBMCs in the presence of IL-2 and OKT3 for 3 weeks. Cell viability was slightly reduced after freezing and thawing, but cytotoxicity and cytokine secretion were not significantly different. In a xenograft mouse model of hepatocellular carcinoma cells, cryopreserved NK cells had slightly lower anti-tumor efficacy than freshly expanded NK cells, but this was overcome by a 2-fold increased dose of cryopreserved NK cells. In vivo antibody-dependent cell cytotoxicity (ADCC) activity of cryopreserved NK cells was also demonstrated in a SCID mouse model injected with Raji cells with rituximab co-administration. Therefore, we demonstrated that expanded/frozen NK cells maintain viability, phenotype, and anti-tumor activity immediately after thawing, indicating that expanded/frozen NK cells can provide ‘ready-to-use’ cell therapy for cancer patients.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Phenotype
/
Killer Cells, Natural
/
Cryopreservation
/
Cell Survival
/
Interleukin-2
/
Muromonab-CD3
/
Mice, SCID
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Carcinoma, Hepatocellular
/
Heterografts
/
Cell- and Tissue-Based Therapy
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Immune Network
Year:
2018
Type:
Article