2004 Fiscal Year Final Research Report Summary
Effect of macrophages transduced with an adenoviral vector expressing interleukin-12 in prostate cancer
| Project/Area Number |
15591712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kitasato University |
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Principal Investigator |
IWAMURA Masatsugu Kitasato University, Medicine, Associate Professor, 医学部, 講師 (20176564)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Takefumi Kitasato University, Medicine, Research associate, 医学部, 助手 (50286332)
IRIE Akira Kitasato University, Medicine, Assistant Professor, 医学部, 講師 (50193694)
MATSUMOTO Kazumasa Kitasato University, Medicine, Research associate, 医学部, 助手 (70306603)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Interleukin-12 / Macrophages / Prostate cancer / Immunomofulatory approaches / 米国 |
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| Research Abstract |
For advanced prostate cancer, the standard therapy is androgen ablation, which largely palliative and it is critical to develop additional therapies that are effective against systemic disease to complement current treatments for localized prostate cancer. Novel approaches, such as immunogene therapy, provide opportunities to achieve these goals.
We investigated the efficacy of macrophages transduced with murine IL-12 recombinant adenoviral vector (AdmIL-12) using the 178-2 BMA mouse prostate cancer model. AdmIL-12-transduced macrophages secreted IL-12 in vitro and there were no significant differences in cell number at any MOI. Uninfected macrophages and Adβgal-infected macrophages produced very low levels of IL-12 at 24h and 48h, whereas a dose- and time- dependent increase in secretion of mIL-12 was detected in the AdmIL-12-infected macrophages. Cytometric analysis showed that AdmIL-12-infected macrophages had an 2 fold increase in surface expression of MHC class I and II molecules and F4/80 antigen compared with uninfected macrophages. Adβgal-infected macrophages were similar to uninfected macrophages except that increased MHC class II expression was observed. According to these results, we have demonstrated successful genetic modification of murine peritoneal exudates macrophages with adenoviral vectors and this therapeutic approach may induced substantial systemic antitumor immunological responses, hopefully. For next step to determine possible therapeutic activities AdmIL-12 transduced macrophages, we are going to set up preclinical experiment using an orthotopic mouse model of metastatic prostate cancer.
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