High frequency of specific CD8(+) T cells in the tumor and blood is associated with efficient local IL-12 gene therapy of cancer

Cancer immunotherapy often aims at the reactivation and expansion of tumor- specific CTL. In an attempt to correlate in situ and/or systemic tumor-spec ific T cell. expansion with tumor regression, we investigated the effects o f adenovirus-mediated IL-12 or IFN-gamma gene transfer into established P81 5 murine tumors. While IFN-gamma was no more potent than the vector alone, IL-12 gene transfer promoted tumor eradication. Despite this antitumor effe ct, no significant cytolytic activity,vas detectable using classical cytoto xicity assays from in vitro restimulated splenocytes, Since intratumor gene delivery may induce a localized expansion of CTL, the presence of P815-spe cific CD8(+) T cells in situ was assessed. Using the Immunoscope approach, we found a dramatic increase in clonotypic T cells at the tumor site follow ing IL-12, but not IFN-gamma gene delivery. Antitumor CD8+ T cell frequenci es were then re-evaluated using this molecular detection technique, which r evealed a comparable expansion of specific T cells in the peripheral organs , most strikingly in the blood. These data show that local IL-12 gene trans fer, in contrast to IFN-gamma, mediates a potent antitumor effect that corr elates to clonal tumor-specific T cell expansions in situ and in the periph ery.