Abstract
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-gamma 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / immunology
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Adenocarcinoma / pathology
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Adenocarcinoma / therapy*
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Animals
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Apoptosis
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Culture Media, Conditioned / pharmacology
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Cytotoxicity, Immunologic / drug effects
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Gene Expression Regulation
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Genes, Synthetic
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Genetic Therapy*
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Human Growth Hormone / genetics
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Interleukin-15 / biosynthesis
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Interleukin-15 / genetics*
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Interleukin-15 / metabolism
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Interleukin-2 / genetics
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Killer Cells, Natural / immunology*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Transplantation
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / therapy*
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Protein Biosynthesis
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Protein Sorting Signals / genetics
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RNA, Messenger / biosynthesis
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / physiology
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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Transfection
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Culture Media, Conditioned
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Interleukin-15
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Interleukin-2
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Protein Sorting Signals
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RNA, Messenger
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Recombinant Fusion Proteins
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Human Growth Hormone
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Interferon-gamma