Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors.
We examined whether antitumor immunity could be generated by the inoculation of cytokine-producing murine neuroblastoma cells (C1300), and whether the immunity might be effective for the established tumors of wild-type (wt) cells. For that purpose, we transduced low immunogenic C1300 cells with interleukin-2 (IL-2), GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngeneic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 cells, although their in vitro growth rates were not affected by the transduction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did not develop tumors of wt cells inoculated subsequently, but formed tumors of irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of IL-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 and in reducing the number of preexisting metastatic foci in the liver. These data suggest a potential application of IL-2- or GM-CSF-producing syngeneic tumor cells for the treatment of low immunogenic neuroblastomas.
Yoshida
H
H
Department of Pediatric Surgery, School of Medicine, Chiba University, Japan.
Tanabe
M
M
Miyauchi
M
M
Kawamura
K
K
Takenaga
K
K
Ohnuma
N
N
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy
D019496:Cancer Vaccines; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor