|Budget Amount *help
¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1998 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1997 : ¥2,700,000 (Direct Cost : ¥2,700,000)
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.