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 C1300 cells (C1300/IL-4) was not different from that of wild-type cells, the in vivo tumor growth of C1300/IL-4 cells subcutaneously inoculated into immunocompetent A/J mice was retarded compared with that of wild-type cells and consequently, the survival of the A/J mice which received C1300/IL-4 cells was prolonged. In immunodeficient nude mice we observed accelerated growth rate of wild-type tumors in comparison with the tumors developed in A/J mice. In contrast, the tumor growth of C1300/IL-4 cells in nude mice was significantly suppressed and the growth was much slower than that of C1300/IL-4 cells inoculated in A/J mice. Thus, the secretion of IL-4 from tumor cells produced antitumor effect more efficiently in mature T cell-defective hosts than in immunocompetent mice. Our results suggest a possible clinical application of IL-4 expression in tumor cells via genetic manipulations especially in immunocompromised cancer patients.