Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors
Purpose: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear factor κB (NFκB), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs). Experimental Design: We used an adenovirus vector encoding only the...
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description | Purpose: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear
factor κB (NFκB), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs).
Experimental Design: We used an adenovirus vector encoding only the RHD of the NFκB (p65 family member) cDNA (AdRHD) to transduce murine 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 interleukin (IL) 1β, IL-6, and IL-12 (p40) compared with sham-transduced
BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers CD40,
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 tumors (CT26 and B16.F10) was inhibited, and survival was prolonged in the mice that received
intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 tumor-bearing animals that received intratumoral
AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host mice
harboring targeted mutations in CD4 and CD8, as well as BMDCs from mice lacking MHC class I, MHC class II, or IL-12 revealed
that this tumor immunity was dependent on the presence of CD4+ and CD8+ cells in the tumor-bearing host, as well as MHC class
I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 (p40) expression by AdRHD
was completely abrogated in BMDCs lacking the c-Rel NFκB family member.
Conclusions: We made the following conclusions: ( a ) gene transfer-mediated overexpression of the RHD of NFκB activates BMDCs; ( b ) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the CD4+ T
cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and ( c ) IL-12 (p40) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the c-Rel NFκB family member. |
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fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72686972</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72686972</sourcerecordid><originalsourceid>FETCH-LOGICAL-h240t-18151f2e3c591e1b0529f88a8f7f74e10da617222204d7ff7a522ad1cfb069063</originalsourceid><addsrcrecordid>eNpNkUtO5DAQhiPEiPcVkFeITSTbie1k2TQ0g8RjNPTMNnI7ZWKUOMGOG-ZqHAKJG-HwEONNWfZXf9VftZHsEMZEmlHONuMdiyLFeUa3k13v7zEmOcH5VrJNaE5Lnoud5HVWg-3XxgWP_oIae5d2UBs5Qo1u1uDgaXDgvekt6jWSaOmCVe-_i95109vYABo4Q9dBtSAdWshJBb08nyB1ej1DxqJTsLUzo1FoDm3r0ZltpFXg0bIBEzOi5DhV-A0-tKOxd1PSRdcFC9_d3Ibh_1Z-OYAn49_pq-CMBbQMXe_8fvJDy9bDwWfcS_4szpbzn-nlzfnFfHaZNjTHY0oKwoimkClWEiArzGipi0IWWmiRA8G15ETQeHBeC62FZJTKmii9wrzEPNtLjj50B9c_BPBj1Rmvoj9poQ--EpQXvBQ0goefYFhFN9XgTCfdv-prCRE4_gAac9c8GgeVmsbjots4UNVURUVIlTFOsjdEXZZD</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72686972</pqid></control><display><type>article</type><title>Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Lee, Jay M ; Mahtabifard, Ali ; Yamada, Reiko ; Crystal, Ronald G ; Korst, Robert J</creator><creatorcontrib>Lee, Jay M ; Mahtabifard, Ali ; Yamada, Reiko ; Crystal, Ronald G ; Korst, Robert J</creatorcontrib><description>Purpose: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear
factor κB (NFκB), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs).
Experimental Design: We used an adenovirus vector encoding only the RHD of the NFκB (p65 family member) cDNA (AdRHD) to transduce murine 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 interleukin (IL) 1β, IL-6, and IL-12 (p40) compared with sham-transduced
BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers CD40,
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 tumors (CT26 and B16.F10) was inhibited, and survival was prolonged in the mice that received
intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 tumor-bearing animals that received intratumoral
AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host mice
harboring targeted mutations in CD4 and CD8, as well as BMDCs from mice lacking MHC class I, MHC class II, or IL-12 revealed
that this tumor immunity was dependent on the presence of CD4+ and CD8+ cells in the tumor-bearing host, as well as MHC class
I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 (p40) expression by AdRHD
was completely abrogated in BMDCs lacking the c-Rel NFκB family member.
Conclusions: We made the following conclusions: ( a ) gene transfer-mediated overexpression of the RHD of NFκB activates BMDCs; ( b ) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the CD4+ T
cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and ( c ) IL-12 (p40) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the c-Rel NFκB family member.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 12429647</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Adenoviridae - genetics ; Animals ; CD11c Antigen - biosynthesis ; CD3 Complex - biosynthesis ; CD4-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - metabolism ; Cytokines - metabolism ; Dendritic Cells - metabolism ; Flow Cytometry ; Gene Transfer Techniques ; Genes, MHC Class I ; Genes, MHC Class II ; Genetic Vectors ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Transplantation ; NF-kappa B - chemistry ; NF-kappa B - genetics ; Peptides - chemistry ; Protein Structure, Tertiary ; Time Factors ; Transcription Factor RelA ; Transfection ; Tumor Cells, Cultured ; Up-Regulation</subject><ispartof>Clinical cancer research, 2002-11, Vol.8 (11), p.3561-3569</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12429647$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jay M</creatorcontrib><creatorcontrib>Mahtabifard, Ali</creatorcontrib><creatorcontrib>Yamada, Reiko</creatorcontrib><creatorcontrib>Crystal, Ronald G</creatorcontrib><creatorcontrib>Korst, Robert J</creatorcontrib><title>Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear
factor κB (NFκB), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs).
Experimental Design: We used an adenovirus vector encoding only the RHD of the NFκB (p65 family member) cDNA (AdRHD) to transduce murine 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 interleukin (IL) 1β, IL-6, and IL-12 (p40) compared with sham-transduced
BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers CD40,
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 tumors (CT26 and B16.F10) was inhibited, and survival was prolonged in the mice that received
intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 tumor-bearing animals that received intratumoral
AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host mice
harboring targeted mutations in CD4 and CD8, as well as BMDCs from mice lacking MHC class I, MHC class II, or IL-12 revealed
that this tumor immunity was dependent on the presence of CD4+ and CD8+ cells in the tumor-bearing host, as well as MHC class
I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 (p40) expression by AdRHD
was completely abrogated in BMDCs lacking the c-Rel NFκB family member.
Conclusions: We made the following conclusions: ( a ) gene transfer-mediated overexpression of the RHD of NFκB activates BMDCs; ( b ) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the CD4+ T
cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and ( c ) IL-12 (p40) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the c-Rel NFκB family member.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>CD11c Antigen - biosynthesis</subject><subject>CD3 Complex - biosynthesis</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Dendritic Cells - metabolism</subject><subject>Flow Cytometry</subject><subject>Gene Transfer Techniques</subject><subject>Genes, MHC Class I</subject><subject>Genes, MHC Class II</subject><subject>Genetic Vectors</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasm Transplantation</subject><subject>NF-kappa B - chemistry</subject><subject>NF-kappa B - genetics</subject><subject>Peptides - chemistry</subject><subject>Protein Structure, Tertiary</subject><subject>Time Factors</subject><subject>Transcription Factor RelA</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkUtO5DAQhiPEiPcVkFeITSTbie1k2TQ0g8RjNPTMNnI7ZWKUOMGOG-ZqHAKJG-HwEONNWfZXf9VftZHsEMZEmlHONuMdiyLFeUa3k13v7zEmOcH5VrJNaE5Lnoud5HVWg-3XxgWP_oIae5d2UBs5Qo1u1uDgaXDgvekt6jWSaOmCVe-_i95109vYABo4Q9dBtSAdWshJBb08nyB1ej1DxqJTsLUzo1FoDm3r0ZltpFXg0bIBEzOi5DhV-A0-tKOxd1PSRdcFC9_d3Ibh_1Z-OYAn49_pq-CMBbQMXe_8fvJDy9bDwWfcS_4szpbzn-nlzfnFfHaZNjTHY0oKwoimkClWEiArzGipi0IWWmiRA8G15ETQeHBeC62FZJTKmii9wrzEPNtLjj50B9c_BPBj1Rmvoj9poQ--EpQXvBQ0goefYFhFN9XgTCfdv-prCRE4_gAac9c8GgeVmsbjots4UNVURUVIlTFOsjdEXZZD</recordid><startdate>20021101</startdate><enddate>20021101</enddate><creator>Lee, Jay M</creator><creator>Mahtabifard, Ali</creator><creator>Yamada, Reiko</creator><creator>Crystal, Ronald G</creator><creator>Korst, Robert J</creator><general>American Association for Cancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20021101</creationdate><title>Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors</title><author>Lee, Jay M ; Mahtabifard, Ali ; Yamada, Reiko ; Crystal, Ronald G ; Korst, Robert J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h240t-18151f2e3c591e1b0529f88a8f7f74e10da617222204d7ff7a522ad1cfb069063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>CD11c Antigen - biosynthesis</topic><topic>CD3 Complex - biosynthesis</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Dendritic Cells - metabolism</topic><topic>Flow Cytometry</topic><topic>Gene Transfer Techniques</topic><topic>Genes, MHC Class I</topic><topic>Genes, MHC Class II</topic><topic>Genetic Vectors</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasm Transplantation</topic><topic>NF-kappa B - chemistry</topic><topic>NF-kappa B - genetics</topic><topic>Peptides - chemistry</topic><topic>Protein Structure, Tertiary</topic><topic>Time Factors</topic><topic>Transcription Factor RelA</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Jay M</creatorcontrib><creatorcontrib>Mahtabifard, Ali</creatorcontrib><creatorcontrib>Yamada, Reiko</creatorcontrib><creatorcontrib>Crystal, Ronald G</creatorcontrib><creatorcontrib>Korst, Robert J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Jay M</au><au>Mahtabifard, Ali</au><au>Yamada, Reiko</au><au>Crystal, Ronald G</au><au>Korst, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2002-11-01</date><risdate>2002</risdate><volume>8</volume><issue>11</issue><spage>3561</spage><epage>3569</epage><pages>3561-3569</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear
factor κB (NFκB), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs).
Experimental Design: We used an adenovirus vector encoding only the RHD of the NFκB (p65 family member) cDNA (AdRHD) to transduce murine 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 interleukin (IL) 1β, IL-6, and IL-12 (p40) compared with sham-transduced
BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers CD40,
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 tumors (CT26 and B16.F10) was inhibited, and survival was prolonged in the mice that received
intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 tumor-bearing animals that received intratumoral
AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host mice
harboring targeted mutations in CD4 and CD8, as well as BMDCs from mice lacking MHC class I, MHC class II, or IL-12 revealed
that this tumor immunity was dependent on the presence of CD4+ and CD8+ cells in the tumor-bearing host, as well as MHC class
I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 (p40) expression by AdRHD
was completely abrogated in BMDCs lacking the c-Rel NFκB family member.
Conclusions: We made the following conclusions: ( a ) gene transfer-mediated overexpression of the RHD of NFκB activates BMDCs; ( b ) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the CD4+ T
cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and ( c ) IL-12 (p40) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the c-Rel NFκB family member.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>12429647</pmid><tpages>9</tpages></addata></record> |
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source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Adenoviridae - genetics Animals CD11c Antigen - biosynthesis CD3 Complex - biosynthesis CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - metabolism Cytokines - metabolism Dendritic Cells - metabolism Flow Cytometry Gene Transfer Techniques Genes, MHC Class I Genes, MHC Class II Genetic Vectors Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasm Transplantation NF-kappa B - chemistry NF-kappa B - genetics Peptides - chemistry Protein Structure, Tertiary Time Factors Transcription Factor RelA Transfection Tumor Cells, Cultured Up-Regulation |
title | Adenovirus Vector-mediated Overexpression of a Truncated Form of the p65 Nuclear Factor κB cDNA in Dendritic Cells Enhances Their Function Resulting in Immune-mediated Suppression of Preexisting Murine Tumors |
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