Activation of Natural killer cells with interleukin 21 in the treatment of preclinical Neuroblastoma model

Neuroblastoma (NB) is one of the most prevalent childrenchr('39')s neoplasm and some of which still do not respond to common treatments and is an ideal candidate for NK cell immune therapy. In this research, we have performed cytokine activation of NKs by using proper interleukins to obtain more cytolysis which was evaluated in vitro and in vivo.

Isolation of NKs from human peripheral blood was performed using CD56 marker via magnetic activated cell sorter (MACS). The IL-2 and IL-15 cytokines were used for proliferation, and IL-21 for activation of cells. The neuroblastoma model was developed using the SK-N-SH cell line in Nude mice. The in vitro effect of the NKs on the two neuroblastoma lines were assessed after activation and via flow cytometry confirmation.

The results showed that at the ratio of 1:10 the IL-21 activated NKs lysed 94% of the SK-N-SH and 91% of the CHLA-255 cell lines (P<0.05), in spite of the only 40% and 38% of lysis for these cell lines without activation (P<0.05), respectively. The NKs activated by IL-21 were able to eliminate 70% (P<0.05) of the xenograft neuroblastoma tumors in nude mice.

The present investigation was showed that the activation of NK cells using IL-21 can be useful in the treatment of neuroblastoma and could be applied in future clinical trials.