Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer

Abstract

Background Adoptive 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. Methods Expanded 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. Results The 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. Conclusion The house-developed method can be a new and effective strategy to prepare clinically applicable NKL for autologous NK cell-based anti-tumor immunotherapy. Electronic supplementary material The online version of this article (10.1186/s12885-019-6034-1) contains supplementary material, which is available to authorized users.

Proteome Analysis of Human Natural Killer Cell Derived Extracellular Vesicles for Identification of Anticancer Effectors

“…However, the scarcity of NK cells in human lymphocytes, their changing phenotype, and their impaired functionality during cancer progression necessitates the development of protocols to activate and expand NK cells to sufficient numbers ex vivo for adoptive transfer [4,5]. We have developed a feeder-free NK cell expansion system where clinically viable NK cells are isolated and cultured from human peripheral blood mononuclear cells (PBMCs) for NK studies [6].…”

Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade

“…Recent research has shown that survival and prognosis of HCC patients is positively correlated with NK cell numbers in blood and tumour tissue (169). Tumour progression of these HCC patients was associated with dysfunction of the tumour-infiltrating NK cells (170), and exhausted tumour-infiltrating NK cells correlate with poor clinical outcome for HCC patients. Importantly, this NK cell exhaustion was reversed by manipulating the TIGIT pathway (171).…”

Application of Immunotherapy in Hepatocellular Carcinoma

“…Autologous NK adoptive immune cells are obtained by stimulating the in vitro expansion of CD56 Birght NK cells in peripheral monocytes with cytokines. NK cells in peripheral blood can proliferate 140 times in a short time by stimulating with some cytokines ( 114 ). Meanwhile, these amplified and activated NK cells show strong anti-tumor effects in vitro and in vivo ( 114 ).…”

“…NK cells in peripheral blood can proliferate 140 times in a short time by stimulating with some cytokines ( 114 ). Meanwhile, these amplified and activated NK cells show strong anti-tumor effects in vitro and in vivo ( 114 ). Nonetheless, the clinical efficacy of autologous NK cells is not significant ( 115 ).…”