Systemic administration of interleukin 2 enhances the therapeutic efficacyof dendritic cell-based tumor vaccines

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune r esponses both in vitro and in vivo. Because successful therapy was dependen t on host immune T cells, we have now evaluated whether the systemic admini stration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sar coma (MCA-207), the systemic administration of nontoxic doses of recombinan t IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant inc reases in the potency of DC-based immunizations. IL-2 could augment the eff icacy of tumor lysate-pulsed DC to induce protective immunity to lethal tum or challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-gamma production in these treated mice. Moreover, treatment wit h the combination of tumor lysate-pulsed DC and IL-2 could also mediate reg ressions of established pulmonary 3-day micrometastases and 7-day macrometa stases as mil as established 14- and 28-day s.c tumors, leading to either s ignificant cure rates or prolongation in overall, survival, Collectively, t hese findings show that nontoxic doses of recombinant IL-2 can potentiate t he antitumor effects of tumor lysate-pulsed DC in ville and provide preclin ical rationale for the use of IL-2 in DC-based vaccine strategies in patien ts with advanced cancer.