IMPAIRED TUMORIGENICITY OF IL-4-PRODUCING MURINE NEUROBLASTOMA-CELLS IN IMMUNODEFICIENT NUDE-MICE

We have examined antitumor effect of murine neuroblastoma cells (C1300 ) retrovirally transduced with interleukin-4 (IL-4) gene in syngeneic A/J and nude mice. Although in vitro proliferation of IL-4-secreting C 1300 cells (C1300/IL-4) was not different from that of wild-type cells , the in vivo tumor growth of C1300/IL-4 cells subcutaneously inoculat ed into immunocompetent A/J mice was retarded compared with that of wi ld-type cells and consequently, the survival of the A/J mice which rec eived C1300/IL-4 cells was prolonged. In immunodeficient nude mice we observed accelerated growth rate of wild-type tumors in comparison wit h the tumors developed in A/J mice. In contrast, the tumor growth of C 1300/IL-4 cells in nude mice was significantly suppressed and the grow th was much slower than that of C1300/IL-4 cells inoculated in A/J mic e. Thus, the secretion of IL-4 from tumor cells produced antitumor eff ect more efficiently in mature T cell-defective hosts than in immunoco mpetent mice. Our results suggest a possible clinical application of I L-4 expression in tumor cells via genetic manipulations especially in immunocompromised cancer patients.