Antimetastatic vaccination against Lewis lung carcinoma with autologous tumor cells modified to express murine Interleukin 12

Interleukin 12 (IL-12) is a disulfide-linked heterodimer molecule produced predominantly by professional antigen presenting cells, It promotes the ind uction of sundry biological effects with significant relevance to antitumor immunity, such as enhancing a T(H)1 helper response, an in vivo antiangiog enic effect, induction of adhesion molecules that assist in lymphocyte homi ng to sites of tumor growth, and a direct stimulatory effect on both T-cell s and NK cells, We tested the efficacy of an antimetastatic vaccine compose d of autologous murine D122 cells transfected with both subunits of IL-12 c DNA to express biologically-active IL,-12 molecule, Expression of IL-12 by D122 cells significantly reduced their tumorigenicity and metastatic potent ial in immunocompetent syngeneic hosts. furthermore, vaccination of mice wi th 2 x 10(6) irradiated IL-12-transfected D122 cells engendered a protectiv e CTL response which rejected a subsequent challenge with parental D122 cel ls and eradicated lung micrometastasis in animals whose primary tumors have been surgically removed. The antitumor effects of IL-12 were mediated prim arily by its ability to induce gamma IFN expression in vivo. CD8+ T-cells a s well as NK cells were crucial in the execution of the antitumor effects o f IL-12, These results suggest that autologous tumor cells expressing IL,-1 2 by gene transfer are a potent antitumor vaccine able to induce a systemic immune response against poorly immunogenic and spontaneously metastatic tu mors.