Tumour cell expression of B7 costimulatory molecules and interleukin-12 or granulocyte–macrophage colony-stimulating factor induces a local antitumour response and may generate systemic protective immunity

Abstract

Previously, we showed that expression of B7–1 in CMT93 murine colorectal tumour cells inhibited their growth in immunocompetent animals. However, this did not result in any significant increase in systemic protective immunity, relative to that elicited by the parental tumour. To potentiate the effects of B7–1 on systemic immunity, interleukin-12 (IL-12) or granulocyte–macrophage colony-stimulating factor (GM-CSF) was co-expressed with this molecule. These combinations of immunostimulatory molecules were effective in eliciting systemic immunity. We also show that expression of B7–2 led to a local antitumour response as well as significantly raised systemic immunity. In another tumour model, K1735 murine melanoma, which is moderately immunogenic, tumours secreting GM-CSF alone were as effective as the parental tumours in generating protective immunity. Previously, we described the deleterious effect of B7–1 expression on protective immunity. Co-expression of GM-CSF did not counteract this consequence of B7–1 expression. Expression of IL-12 was extremely effective in causing rejection of inoculated tumour cells, but evoked only minimal protective systemic immunity. These results suggest that combining costimulatory molecules and cytokines may be a useful therapeutic approach in some, but not all, tumours.