NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer

Interleukin (IL)‐15 is a pleiotropic cytokine that is important forinnate and adaptive immune cell homeostasis. The expression of IL‐15protein is controlled by posttranscriptional mechanisms. Here, weconstructed a human IL‐15 expression vector consisting of the humanIL‐2 signal peptide, the human IL‐15 mature peptide‐coding sequences,and an out‐of‐frame human growth hormone gene. Human prostate cancercells, PC‐3, transfected with this highly secretable form of the IL‐15gene, successfully secreted abundant bioactive IL‐15 protein. In nudemice, the growth of PC‐3 cells producing IL‐15 was remarkably retarded.NK cell‐depletion using anti‐asialo GM1 antibody restoredtumorigenicity. Histologically, tumors derived from IL‐15‐producingPC‐3 cells contained necrotic areas with high apoptotic index.Splenocytes incubated with supernatant of transfectants killed targetPC‐3 cells and expressed a significantly high level of mIFN‐γ mRNA.These observations suggest that NK cell‐mediated, anti‐tumor effects ofIL‐15 could provide a potential rationale for gene therapy of prostatecancer.