2002 Fiscal Year Final Research Report Summary
Bystander effect of IL-12 and P53 gene therapy in the head and neck
| Project/Area Number |
13671792
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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 |
Otorhinolaryngology
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| Research Institution | Department of Otolaryngology, Yokohama City University School of Medicine |
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Principal Investigator |
TSUKUDA Mamoru Dept. of Otolaryngology, Yokohama City University School of Medicine, 医学部, 教授 (70142370)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Yasuhiro Dept. of Otolaryngology, Yokohama City University School of Medicine, 講師 (20305478)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Head and Neck Ca. / Gene Therapy / IL-12 gene / Anti-tumor effects / Mechanism |
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| Research Abstract |
The research was mainly focused on IL-12 gene therapy. Human KB cells transfected hIL-12 gene(KB/IL-12) produced IL-12 in the culture supernatant. KB/IL-12 cells showed a strong anti-tumor potential through elevated immunity. On the other hand direct administration of mIL-12 gene to inoculated tumors with NR-S1 (murine oral carcinoma) resulted in IFN-γ production and anti-tumor effects. The mRNA expression of VEGF in NR-S1 cells transfected with mIL-12 gene decreased significantly, compared to non-treated NR-S1 cells.
Furthermore, combined treatment with IL-12 gene therapy and chemotherapy, e. g. CDDP or UFT, showed a compete response in the murine model. The mechanisms of anti-tumor effects were considered to be induction of apoptosis, ant angiogenesis, immunological enhancement with the accumulation of CD8+ and CD56+ in the tumor site and synergistic effects of both treatments, especially immunological augmentation of IL-12 gene therapy on the deteriorated immunity by chemotherapy.
In ELISPOT analysis, IFN-γ positive spleen cells increased in the mice group receiving IL-12 gene therapy, compared to those in the control one. This result showed Th_1 predominant condition caused by IL-12 gene therapy.
In conclusion, IL-12 gene therapy not only augments local and systemic immunity and induce apoptotic change of tumor cells, but also suppresses angiogenesis of tumors, resulting in anti-tumor effects through comprehensive mechanisms.
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