Department of Urology, Gunma University School of Medicine, Maebashi, Japan
Correspondence: Kazuhiro Suzuki, M.D., Department of Urology, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, 371-8511, Japan. E-mail: kazu{at}showa.gunma-u.ac.jp
Interleukin (IL)-15 is a pleiotropic cytokine that is important for
innate and adaptive immune cell homeostasis. The expression of IL-15
protein is controlled by posttranscriptional mechanisms. Here, we
constructed a human IL-15 expression vector consisting of the human
IL-2 signal peptide, the human IL-15 mature peptide-coding sequences,
and an out-of-frame human growth hormone gene. Human prostate cancer
cells, PC-3, transfected with this highly secretable form of the IL-15
gene, successfully secreted abundant bioactive IL-15 protein. In nude
mice, the growth of PC-3 cells producing IL-15 was remarkably retarded.
NK cell-depletion using anti-asialo GM1 antibody restored
tumorigenicity. Histologically, tumors derived from IL-15-producing
PC-3 cells contained necrotic areas with high apoptotic index.
Splenocytes incubated with supernatant of transfectants killed target
PC-3 cells and expressed a significantly high level of mIFN-
mRNA.
These observations suggest that NK cell-mediated, anti-tumor effects of
IL-15 could provide a potential rationale for gene therapy of prostate
cancer.
Key Words: cellular immunity • chimeric peptide • murine IFN • anti-asialo GM1
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