Adenovirus-mediated @entity42201 gene transfer improves therapeutic efficacy of @entity5538 deaminase suicide gene therapy in established @entity19 XXXX .

@entity2047 @entity19 @entity8271 @entity5 @entity4895 @entity60 @entity1309 @entity5538 @entity8024 @entity694 @entity42201
@entity42201 ( @entity42201 ) is the sole member of C chemokines which attracts T cells and NK cells specially. @entity42201 gene was transferred in vivo to improve the antitumor efficacy of @entity5538 deaminase (CD) gene therapy. Upregulation of @entity8271 and @entity8024 on @entity19 CT26 @entity694 cells was observed after combined transfection with adenovirus encoding CD (AdCD) and adenovirus encoding @entity19 @entity42201 (AdLtn) followed by administration of @entity4895 (5FC) in vitro. AdCD/5FC treatment also increased the expression of @entity1309 and induced obvious apoptosis of CT26 cells. After combined treatment with AdLtn and AdCD/5FC, the pre-established @entity19 model with subcutaneous CT26 @entity694 exhibited most significant @entity5 growth inhibition, and four of @entity5 -bearing @entity19 were @entity5 free, while @entity5 in other @entity19 grew more progressively. Examination of lymphocyte infiltration and cytokine gene expression in @entity5 tissue revealed that @entity5 from AdLtn/AdCD/5FC-or AdLtn-treated @entity19 were heavily infiltrated with CD4+, CD8+ T cells and NK cells, and @entity2047 and @entity60 mRNA expression were present in parallel with T cell and NK cell infiltration. Splenic NK and CTL activities increased significantly after the combination therapy. In vivo depletion analysis showed that NK cells, CD4+ T cells and CD8+T cells participated in the antitumor effect of the host with CD8+T cells being the main T cell subset responsible for the enhanced antitumor immune response. These findings suggested that increased immunogenicity and induction of apoptosis of the @entity5 cells, and efficient induction of local and systemic antitumor immunity of the host might contribute to the enhanced antitumor effects of the combined @entity42201 and CD suicide therapy. Gene Therapy (2000) 7, 329-338.
