H. Yoshida et al., Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors, CANC GENE T, 6(5), 1999, pp. 395-401
We examined whether antitumor immunity could be generated by the inoculatio
n of cytokine-producing murine neuroblastoma cells (C1300), and whether the
immunity might be effective for the established tumors of wild-type (wt) c
ells. For that purpose, we transduced low immunogenic C1300 cells with inte
rleukin-2 (IL-2) GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngene
ic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 c
ells, although their in vitro growth rates were not affected by the transdu
ction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did no
t develop tumors of wt cells inoculated subsequently, but formed tumors of
irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of I
L-2 or GM-CSF producers into immunocompetent mice generated tumor-specific
acquired immunity. The induced immunity using IL-2 or GM-CSF producers was
also effective in eradicating established subcutaneous tumors of wt cells a
nd in reducing the number of preexisting metastatic foci in the liver. Thes
e data suggest a potential application of IL-2- or GM-CSF-producing syngene
ic tumor cells for the treatment of low immunogenic neuroblastomas.