title: GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.
abstract: Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3(+) T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(-)CD16(+)CD56(+) NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.
authors: BioMedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, Republic of Korea.
authors: Okjae
authors: O
authors: Lim
authors: Yuna
authors: Y
authors: Lee
authors: Hyejin
authors: H
authors: Chung
authors: Jung Hyun
authors: JH
authors: Her
authors: Sang Mi
authors: SM
authors: Kang
authors: Mi-young
authors: MY
authors: Jung
authors: Bokyung
authors: B
authors: Min
authors: Hyejin
authors: H
authors: Shin
authors: Tae Min
authors: TM
authors: Kim
authors: Dae Seog
authors: DS
authors: Heo
authors: Yu Kyeong
authors: YK
authors: Hwang
authors: Eui-Cheol
authors: EC
authors: Shin
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods* / Q000592:standards*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D055607:Receptors, Natural Killer Cell / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: D055607:Receptors, Natural Killer Cell