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. 1994 Feb;15(2):119-28.
doi: 10.1097/00002371-199402000-00005.

Production of interleukin-2 by EL4 tumor cells induces natural killer cell- and T-cell-mediated immunity

M J Visseren  1 , M Koot, E I van der Voort, L A Gravestein, H J Schoenmakers, W M Kast, M Zijlstra, C J Melief
Affiliations

Production of interleukin-2 by EL4 tumor cells induces natural killer cell- and T-cell-mediated immunity

M J Visseren et al. J Immunother Emphasis Tumor Immunol. 1994 Feb.

Abstract

Systemic administration of recombinant interleukin (rIL)-2 to cancer patients has met with limited clinical success since, despite significant antitumor effects, its use is associated with severe toxicity. Local production of IL-2 by IL-2 gene transfected tumor cells in murine model systems has been reported to induce specific immunity--devoid of toxicity--to the parental non-IL-2-producing tumor cells. We now report enhanced resistance in nonimmunized mice to murine EL4 thymoma cells, producing murine IL-2 following gene transfer (EL4pIL-2). This effect is mediated by activated natural killer (NK) cells, since we observed the same effect in nude mice but not in NK-depleted mice. Additionally, in mice repeatedly vaccinated with irradiated EL4pIL-2 cells, we observed immunity to challenge with a tumorigenic dose of EL4 cells transfected with a control vector, EL4p. EL4-specific cytotoxic T-lymphocytes (CTLs) were detected in these mice. Mice vaccinated with irradiated EL4p cells were less protected against challenge with a tumorigenic dose of EL4p cells. This study indicates that although some IL-2-producing autologous tumor cells elicit NK-mediated responses and not CTL responses upon inoculation, tumor-specific CTL responses are generated upon repeated vaccinations with these cells. This strategy has potential application for treating a wide variety of cancer patients with autologous IL-2 producing tumor cells.

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