Interleukin 1 as an adjuvant for active specific immunotherapy in a murine tumor model

Many vaccines are dependent on adjuvants to augment the immunizing process. The vaccines being developed for active specific immunotherapy of cancer have also usually included an adjuvant in the clinical studies. Several cytokines have been identified which are participants in the immune response to new antigenic stimulation. We investigated the potential of interleukin 1 (IL-1) to serve as an adjuvant when administered either locally with the vaccine or given systemically. Using a weakly immunogenic syngeneic murine lung cancer tumor system (Line 1, BALB/cByJ mice), we have administered recombinant human IL-1 alpha, recombinant human IL-1 beta, and the peptide fragment 163-171 of IL-1 beta in combination with a vaccine of radiated tumor cells. We demonstrated an improved vaccine effectiveness with all three types of IL-1 molecules. The effect was both dose dependent and duration dependent (the number of daily doses given). When IL-1 was administered at a site remote from the vaccine, it functioned as well as when administered at the vaccine site indicating that IL-1 functions as a systemic adjuvant. A requirement for administering the IL-1 during the 10-day period following the vaccine, rather than later, was observed. A detrimental effect on weight gain was seen with high doses of IL-1 alpha, IL-1 beta, and the peptide but some lower doses were effective in the adjuvant function without impairing weight gain. When eight daily doses of IL-1 were given following the vaccine, 70-100% of the mice became tumor free, while mice receiving vaccine alone were only 0-20% tumor free. We conclude that IL-1 appears promising as an adjuvant to vaccines and is highly effective in this model of active specific immunotherapy for cancer.