Supercharged natural killer (NK) cells inhibit melanoma tumor progression and restore endogenous NK cell function in humanized BLT mice

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Abstract

We have previously shown that a single infusion of supercharged NK cells (sNK) was able to significantly decrease or eliminate oral, pancreatic, and uterine cancers implanted in hu-BLT mice. In this report, we extended those studies to melanoma tumors to observe whether there were differences in response to sNK cells. Furthermore, we studied the effect of sNK cell therapy on PBMCs, bone marrow, and spleen of hu-BLT mice. Our studies indicated that infusion of super-charged NK cells inhibited melanoma tumor growth in hu-BLT mice. In addition, sNK cells circulated through PBMCs, spleen, and bone marrow, and they were also found within the tumor of hu-BLT mice. Moreover, the sNK cells were responsible for the induction of in vivo differentiation of the melanoma tumors. sNK cell infusion increased percentages of NK cells in PBMCs of hu-BLT mice, and restored cytotoxicity and IFN-γ secretion within the PBMCs, spleen, and bone marrow of melanoma tumor-bearing mice. Overall, these results suggested that sNK cell therapy is efficacious in limiting melanoma tumor growth and should be considered as a cell therapy to stop or eliminate these tumors in patients. In addition, sNK cells, by increasing the levels and function of autologous NK cells, should be able to restore the inactivated function of NK cells by the tumor cells in cancer patients.

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