International immunopharmacology · 2025
A rapid ex vivo co-culture of memory-like NK and activated T cells enhances anti-tumor response in gastric cancer.
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Chen Wenxiu, Tian Manman, Shen Jie, Liu Qin, Li Rutian, Liu Baorui, Shao Jie
Аннотация
BACKGROUND: Adoptive transfer of NK or T cells alone requires a long preparation time. We developed a rapid co-culture system, including cytokine-induced memory-like NK (CIML NK) cells and activated T cells (Ac-T), as well as tumor-penetrating peptide iRGD.
METHODS: PBMCs were pretreated with IL-12/15/18 for 16 h, then washed to induce a memory NK phenotype. K562-CD48-41BBL-mbIL-21 cells were generated by lentiviral transduction and used as feeder cells to expand and activate NK cells from PBMCs for 7 days. On day 7, an anti-CD3 monoclonal antibody (OKT3) and an anti-CD28 monoclonal antibody (CD28.2) were added and washed overnight for 24 h. The in vitro (cytotoxicity, cytokines) and in vivo (tumor inhibition, survival) functions of iRGD-modified CIML NK&Ac-T cells (CIML NK&Ac-T-iRGD) were compared to CIML NK&T-iRGD without addition of CD3/CD28.
RESULTS: We established a one-week rapid co-culture system comprising NK and T cells. This system markedly increased cytokine secretion and demonstrated potent in vitro cytotoxicity against gastric cancer cell lines, significantly inhibited tumor growth, and prolonged survival in a gastric cancer xenograft model. Notably, iRGD-modified CIML NK&Ac-T cells showed superior efficacy compared with CIML NK&T cells.
CONCLUSION: Our data suggest that the rapid co-culture system of iRGD-modified CIML NK&Ac-T cells used for adoptive cell transfer demonstrates potent anti-tumor effects in gastric cancer. This approach is time-efficient and cost-saving, with potential for broader clinical application compared with conventional NK cell therapies.
METHODS: PBMCs were pretreated with IL-12/15/18 for 16 h, then washed to induce a memory NK phenotype. K562-CD48-41BBL-mbIL-21 cells were generated by lentiviral transduction and used as feeder cells to expand and activate NK cells from PBMCs for 7 days. On day 7, an anti-CD3 monoclonal antibody (OKT3) and an anti-CD28 monoclonal antibody (CD28.2) were added and washed overnight for 24 h. The in vitro (cytotoxicity, cytokines) and in vivo (tumor inhibition, survival) functions of iRGD-modified CIML NK&Ac-T cells (CIML NK&Ac-T-iRGD) were compared to CIML NK&T-iRGD without addition of CD3/CD28.
RESULTS: We established a one-week rapid co-culture system comprising NK and T cells. This system markedly increased cytokine secretion and demonstrated potent in vitro cytotoxicity against gastric cancer cell lines, significantly inhibited tumor growth, and prolonged survival in a gastric cancer xenograft model. Notably, iRGD-modified CIML NK&Ac-T cells showed superior efficacy compared with CIML NK&T cells.
CONCLUSION: Our data suggest that the rapid co-culture system of iRGD-modified CIML NK&Ac-T cells used for adoptive cell transfer demonstrates potent anti-tumor effects in gastric cancer. This approach is time-efficient and cost-saving, with potential for broader clinical application compared with conventional NK cell therapies.