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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(s) -
Suzuki Kazuhiro,
Nakazato Haruki,
Matsui Hiroshi,
Hasumi Masaru,
Shibata Yasuhiro,
Ito Kazuto,
Fukabori Yoshitatsu,
Kurokawa Kohei,
Yamanaka Hidetoshi
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.4.531
Subject(s) - biology , interleukin 15 , immune system , transfection , cancer research , microbiology and biotechnology , cytokine , cell , cell culture , immunology , interleukin , genetics
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.