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We examined the possibility of the use of the IL-4 gene in cancer immuno-gene therapy protocols. Colon carcinoma cell (colon 26) clones engineered to express IL-4 were established. Expression of IL-4 significantly reduced tumorigenicity of colon 26 cells. Administration of anti-IL-4 antibody reversed the non-tumorigenic phenotype of the cells. Mice immunized with MMC-treated IL-4 positive cells rejected challenging IL-4 negative colon 26 cells. Strong CTL responses against colon 26 cells were observed in immunized mice. The lytic activity was tumor specific, and was blocked by the antibody against CD8. Histological examination showed that extensive infiltration of eosinophils occurred on day 5 after inoculation, while lymphocytes became the majority of the infiltrating cells on day 8. These results indicate that the expression of IL-4 in colon 26 cells can induce both eosinophil mediated local tumor killing and T-cell mediated systemic immunity in vivo. The dual mode of action of IL-4 may provide a basis for the advantage of IL-4 secrating tumor cells to apply in the cancer immuno-gene therapy.

Expression of interleukin-4 in colon 26 cells induces both eosinophil mediated local tumor killing and T-cell mediated systemic immunity in vivo.