Adenovirus vector-mediated overexpression of a truncated form of the XXXX nuclear factor kappa B cDNA in dendritic cells enhances their function resulting in immune-mediated suppression of preexisting @entity19 @entity5 .

@entity1992 @entity1991 @entity12782 @entity19 @entity635 @entity5 @entity14636 @entity777 @entity1961 @entity16181
PURPOSE: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear factor kappa B ( @entity1991 ), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs). EXPERIMENTAL DESIGN: We used an adenovirus vector encoding only the RHD of the @entity1991 ( @entity1992 family member) cDNA (AdRHD) to transduce @entity19 BMDCs ex vivo. Endpoints measured included BMDC expression of activation markers, cytokine secretion, peptide antigen presentation, and the ability of these transduced cells to induce antitumor immunity in vivo. RESULTS: AdRHD-transduced BMDCs secreted higher levels of the cytokines @entity635 , @entity777 , and IL-12 ( @entity12782 ) compared with sham-transduced BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers @entity14636 , B7.1, B7.2, and MHC class II on BMDCs, and these cells were able to present a peptide antigen to a T-lymphocyte hybridoma more efficiently than controls in vitro. Growth of syngeneic, established @entity5 (CT26 and B16.F10) was inhibited, and survival was prolonged in the @entity19 that received intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 @entity5 -bearing animals that received intratumoral AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host @entity19 harboring targeted mutations in @entity1961 and CD8, as well as BMDCs from @entity19 lacking MHC class I, MHC class II, or IL-12 revealed that this @entity5 immunity was dependent on the presence of @entity1961 + and CD8+ cells in the @entity5 -bearing host, as well as MHC class I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 ( @entity12782 ) expression by AdRHD was completely abrogated in BMDCs lacking the @entity16181 @entity1991 family member. CONCLUSIONS: We made the following conclusions: (a) gene transfer-mediated overexpression of the RHD of @entity1991 activates BMDCs; (b) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the @entity1961 + T cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and (c) IL-12 ( @entity12782 ) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the @entity16181 @entity1991 family member.
