Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy
Immune Network
;
: e31-2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-716248
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fenótipo
/
Células Matadoras Naturais
/
Criopreservação
/
Sobrevivência Celular
/
Interleucina-2
/
Muromonab-CD3
/
Camundongos SCID
/
Carcinoma Hepatocelular
/
Xenoenxertos
/
Terapia Baseada em Transplante de Células e Tecidos
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Immune Network
Ano de publicação:
2018
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS