Mounting evidence has demonstrated that CD4(+) T cells play an important role in anti-
tumor immune responses. Thus, adoptive transfer of these cells may have great potential for anti-
cancer therapy. However, due to the difficulty to generate sufficient
tumor-specific CD4(+) T cells, the use of CD4(+) T cells in
tumor therapy is limited. It has been found that
IL-15 transfection enhances the proliferation and anti-
tumor activity of
tumor-specific CD8(+) T cells, but the effect of
IL-15 transfection on CD4(+) T cells remains unknown. Here, the effects of retrovirus-mediated
IL-15 expression in Ova-specific CD4(+) T cells from Do11.10 mice were evaluated and it was discovered that
IL-15 transfected CD4(+) T cells expressed both soluble and membrane-bound
IL-15. Retrovirus-mediated
IL-15 expression led to a selective expansion of
antigen-specific CD4(+) T cells by inhibiting their apoptosis. In vivo
IL-15 transfected CD4(+) T cells were more effective in suppressing
tumor growth than control retroviral vector transfected ones. To ensure the safety of the method, the employment of
thymidine kinase gene made it possible to eliminate these transgenic CD4(+) T cells following
ganciclovir treatment. Together, we show that
IL-15 transfection induced a selective expansion of
antigen-specific CD4(+) T cells ex vivo and enhanced their
tumor-suppression effects in vivo. This has an important significance for improving the efficacy of adoptive T cell
therapy.