TUMOR-CELL EXPRESSION OF B7 COSTIMULATORY MOLECULES AND INTERLEUKIN-12 OR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INDUCES A LOCAL ANTITUMOR RESPONSE AND MAY GENERATE SYSTEMIC PROTECTIVE IMMUNITY

Previously, we showed that expression of B7-1 in CMT93 murine colorect al tumour cells inhibited theor growth in immunocompetent animals. How ever, this did not result in any significant increase in systemic prot ective immunity, relative to that elicited by the parental tumour. To potentiate the effects of B7-1 on systemic immunity, interleukin-12 (I L-12) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was co-expressed with this molecule. These combinations of immunostimulat ory molecules were effective in eliciting systemic immunity. We also s how that expression of B7-2 led to a local antitumour response as well as significantly raised systemic immunity. In another tumour model, K 1735 murine melanoma, which is moderately immunogenic, tumours secreti ng GM-CSF alone were as effective as the parental tumours in generatin g protective immunity. Previously, we described the deleterious effect of B7-1 expression on protective immunity. Co-expression of GM-CSF di d 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 res ults suggest that combining costimulatory molecules and cytokines may be a useful therapeutic approach in some, but not all, tumours.