1998 Fiscal Year Final Research Report Summary
Immunogene therapy for the gostrointestinal malignancies using tumor cells engineered to secrete cytokines and chemokines
| Project/Area Number |
09470268
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
HAZAMA Shoich Yamaguchi Univ.Sch.of Med, assistant, 医学部, 助手 (50253159)
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| Co-Investigator(Kenkyū-buntansha) |
OKA Masaaki Yamaguchi Univ.Sch.of Med, professor, 医学部, 教授 (70144946)
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| Project Period (FY) |
1997 – 1998
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| Keywords | IL-15 / IL-18 / GM-CSF / MIP-1alpha / gene therapy / cytokine / chemokine |
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| Research Abstract |
We examined the effect of IL-15, IL-18, GM-CSF, and MIP-1alpha gene transfer into tumor cells on the host's anti-tumor response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8+ T cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells.
In BALB/c mice IL-18 producing colon 26 cells (mature JL-18/colon 26) underwent complete rejection, in a response characterized by massive infiltration of CD8 + T cells and macro phage. In contrast, colon26 cells transfected with control vector (colon26/control) grew rapidly. Moreover, rechallenged parental cells also were rejected. On the other hand, Rechallenged another cancer cell (Meth A ; Methylcorantrain induced sarcoma) were not rejected.
Next, we examine the effect of multiple cytokine producing tumor cells . Tumors which secrete four kinds of cytokines (IL-15, IL-18, GM-CS F, and MIP-1alpha) were injected subcutaneously of syngeneic mice. These results demonstrate that co-injection of IL-15, IL-18 and GM-CS F secreting tumor cells can stimulate strongest local and systemic T cell-dependent immune reaction.
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