Increased understanding of the immune response and, in particular, the biochemical pathways that regulate immunity provide the basis for renewed efforts to develop cancer vaccines. We have developed a syngeneic cell-based anti-leukemia murine model focused on the expression of IL-12 derived from lentiviral transductions. In that work we showed that syngeneic leukemia cells expressing IL-12 can induce protective, long-lasting and specific immunity. Of interest for clinical application, we also demonstrated that as few as 0.5% of the leukemia cells have to express IL-12 to achieve immunity, as long as each cell produces IL-12 above a certain threshold. Once initiated, the immune response it is effective against all of the leukemia cells, including those that do not express IL-12. Using in vivo and in vitro culture systems we are determining the cells required to initiate immunity and target and kill leukemia cells. This work is being extended to solid tumours as well. In addition, these techniques are now being modified using primary human leukemia cell blasts from AML, ALL, CML, and CLL in experiments which form the basis for subsequent human clinical trials.