IMPAIRED TUMORIGENICITY AND DECREASED LIVER METASTASIS OF MURINE NEUROBLASTOMA-CELLS ENGINEERED TO SECRETE INTERLEUKIN-2 OR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

We have examined the antitumor effect of murine neuroblastoma cells (C 1300) engineered to produce cytokines. Retrovirally transduced cells w ith human interleukin-2 (IL-2) or murine GM-CSF gene, but not murine I L-4 gene, abolished their tumorigenicity in syngeneic mice, although t heir in vitro growth rate and expression of class I antigens of the ma jor histocompatibility complex were unchanged. Inoculation of wild-typ e cells into the mice, which had rejected IL-2 or CM-CSF producers, di d not develop tumors, indicating that protective immunity was induced. In an experimental hematogenous metastasis model, we found that the n umbers of metastatic foci in the liver caused by intravenous administr ation of IL-2 or GM-CSF producers were significantly reduced compared with those by the injection of wild-type or vector virus-transduced ce lls. No significant differences in their adhesiveness to extracellular matrices and ability to differentiate were observed among parent and transduced cells. Thus, these results indicate that IL-2 or CM-CSF sec retion, in the vicinity of neuroblastoma cells, produced antitumor eff ect and reduced metastatic ability.