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Laboratoire de Vectorologie et Transfert de Gènes, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 1582, Institut Gustave Roussy, Villejuif, France;
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale Unité 277, Institut Pasteur, Paris, France
Cancer immunotherapy often aims at the reactivation and expansion
of tumor-specific CTL. In an attempt to correlate in situ and/or
systemic tumor-specific T cell expansion with tumor regression, we
investigated the effects of adenovirus-mediated IL-12 or IFN-
gene
transfer into established P815 murine tumors. While IFN- was no more
potent than the vector alone, IL-12 gene transfer promoted tumor
eradication. Despite this antitumor effect, no significant cytolytic
activity was detectable using classical cytotoxicity assays from in
vitro restimulated splenocytes. Since intratumor gene delivery may
induce a localized expansion of CTL, the presence of P815-specific
CD8+ T cells in situ was assessed. Using the Immunoscope
approach, we found a dramatic increase in clonotypic T cells at the
tumor site following IL-12, but not IFN- gene delivery. Antitumor
CD8+ T cell frequencies were then re-evaluated using this
molecular detection technique, which revealed a comparable expansion of
specific T cells in the peripheral organs, most strikingly in the
blood. These data show that local IL-12 gene transfer, in contrast to
IFN-, mediates a potent antitumor effect that correlates to clonal
tumor-specific T cell expansions in situ and in the
periphery.
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