1994 Fiscal Year Final Research Report Summary
Gene therapy for urological cancer by IFN-gamma gene transduction
| Project/Area Number |
05671313
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HASHIMURA Takayuki KYOTO UNIVERSITY,Faculty of Medicine, Associate Professor, 医学部, 講師 (40189478)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Yoichi KYOTO UNIVERSITY,Faculty of Medicine, Instructor, 医学部, 助手 (10243031)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Gene therapy / Bladder cancer / Interferon-gamma / Retro virus / MBT-2 / Class I MHC / CD8(+) T-cell |
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| Research Abstract |
Mouse IFN-gamma gene was transfered into mouse bladder cancer cells (MBT2) by retroviral vector and the IFN-gamma producing cell line, MBT2 (Kgamma), was established. Tumor formations were not observed in mice injected subcutaneouslly with 1.5x105 MBT2 (Kgamma). Furthermore, mice that rejected MBT2 (Kgamma) became highly resistant to a subsequent challenge with parental MBT2, but not to C3H8.2 fibrosarcoma cells. The spleen cells derived from the immunized mice showed the populations of CD8+ effectorT cells against MBT2, which suggests the induction of specific antitumor immunity. For the clinical application of the cytokine gene therapy, the experiment of in vivo direct IFN-gamma gene transfer to MBT2 tumors was performed. After the subcutaneous inoculation of 1.5x105 MBT2 cells into mice, virus culture supernatant containing IFN-gamma gene, psi2 (Kgamma) or psi2 (Mugamma), was injected into the same tumor site once a day for 3 days. In about 40% of mice of treatment of groups with psi2 (Kgamma) or psi2 (Mugamma), tumor formations were not observed. Tumor free survivals and actuarial survivals in the both treatment groups were significantly longer than those of control group. These results showed the possibility of in vivo direct IFN-gamma gene transfer into tumors and were encouraging for the promising execution of tumor cell-targeted IFN-gamma gene therapy against human bladder cancer.
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