C-Glycosphingolipids with an exo-methylene substituent: stereocontrolled synthesis and immunostimulation of mouse and human natural killer T lymphocytes.
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ABSTRACT:
SUBMITTER: Liu Z
PROVIDER: S-EPMC3438909 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
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C-Glycosphingolipids with an exo-methylene substituent: stereocontrolled synthesis and immunostimulation of mouse and human natural killer T lymphocytes.
Liu Zheng Z Courtney Amy N AN Metelitsa Leonid S LS Bittman Robert R
Chembiochem : a European journal of chemical biology 20120710 12
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Project description:BackgroundAdoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a targeted method of controlling the immune system against cancer. Despite their significant therapeutic potential, efficient methods to generate adequate numbers of NK cells are lacking and ex vivo-expansion and activation of NK cells is currently under intensive investigation. The primary purpose of this study was to develop an effective method for expansion and activation of the effector cells with high proportion of NK cells and increasing cytotoxicity against liver cancer in a short time period.MethodsExpanded NK cell-enriched lymphocytes (NKL) designated as "MYJ1633" were prepared by using autologous human plasma, cytokines (IL-2, IL-12 and IL-18) and agonistic antibodies (CD16, CD56 and NKp46) without an NK cell-sorting step. The characteristics of NKL were compared to those of freshly isolated PBMCs. In addition, the cytotoxic effect of the NKL on liver cancer cell was examined in vitro and in vivo.ResultsThe total cell number after ex vivo-expansion increased about 140-fold compared to that of freshly isolated PBMC within 2 weeks. Approximately 78% of the expanded and activated NKL using the house-developed protocol was NK cell and NKT cells even without a NK cell-sorting step. In addition, the expanded and activated NKL demonstrated potent cytotoxicity against liver cancer in vitro and in vivo.ConclusionThe house-developed method can be a new and effective strategy to prepare clinically applicable NKL for autologous NK cell-based anti-tumor immunotherapy.
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