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  • Title: 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.
    Author: Suzuki K, Nakazato H, Matsui H, Hasumi M, Shibata Y, Ito K, Fukabori Y, Kurokawa K, Yamanaka H.
    Journal: J Leukoc Biol; 2001 Apr; 69(4):531-7. PubMed ID: 11310838.
    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.
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