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(Journal of Leukocyte Biology. 2001;69:531-537.)
© 2001 by Society for Leukocyte Biology

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

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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