Transduction of tumor cells with the gene encoding IL-2 enables the tumor cells to secrete high levels of this T-cell stimulatory cytokine. This in turn could stimulate neighboring T-cells, producing a paracrine effect that may enhance development of antitumor immunity. Early studies in mice demonstrated that plasmacytomas transduced to express IL-2 were better able to induce antitumor immunity than nontransduced plasmacytoma cells (54,55).
Recently, Takahashi and colleagues (56) examined whether adenovirus-encoding IL-2 (Ad-IL2) could enhance the ability of CLL cells to stimulate autologous T-cells. Although it was less effective than transduction with adenovirus encoding the ligand for CD40 (CD40L or CD154)
(57), transduction of CLL cells with Ad-IL2 was effective in inducing some T-cell stimulation. Furthermore, a mixture of leukemia cells transduced with Ad-IL2 with cells expressing CD154 induced greater in vitro activation of autologous T-cells against leukemia cells than could either stimulator population alone. Conceivably, co-transduction of leukemia cells with Ad-IL2 along with vectors encoding CD154 could have a greater capacity to induce autologous immune activation in vivo.
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