Comparison of cytokines and CD80 for enhancement of immunogenicity of cervical cancer cells

Tumor cells fail to activate specific cytotoxic T lymphocytes due to lack o f costimulatory molecules e.g. CD80 (B7.1). We were able to render cervical carcinoma cells immunogenic by introduction of the CD80 gene into the tumo r cells. In order to enhance the efficiency of T cell activation we investi gated whether addition of interleukins would augment immunostimulation by C D80. To this end, allogeneic T cells were stimulated with CD80-expressing H eLa cells or CaSki cells in the absence or presence of IL-2, IL-7, IL-12, o r combinations thereof. The proliferative response of the T cells was deter mined. CD80-transduced HeLa or CaSki cells induced a stronger proliferative response in allogeneic T cells than parental or mock transfected control c ells. All three interleukins enhanced the proliferative response of allogen eic T cells to CD80-expressing tumor cells. IL-2 or IL-7 had stronger effec ts in expanding the T cells than IL-12. Combination of IL-2 and IL-7 result ed in best T cell expansion. The proliferating T cells were mainly CD8(+) c ells with MHC class I restricted and unrestricted cytotoxic activity. Stimu lation with CD80 alone or in combination with IL-7 induced mainly cytotoxic T lymphocytes. IL-2, IL-12 or the combination of IL-2 and IL-7 induced nat ural killer cell-like activity and specific cytolytic activity against pare ntal and CD80-positive tumor cells. Our data suggest that the expression of both CD80 and IL-2 plus IL-7 can enhance the efficacy of tumor vaccines.