Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats

Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagoni...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Wang, Fang [verfasserIn] Yu, Jiyun Wang, Yu Jiang, Yunbo Guo, Ning Zhang, Wei

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Rheumatoid arthritis Combination therapy CTLA4-FasL TNFR-Fc

Anmerkung:	© Springer-Verlag Berlin Heidelberg 2015

Übergeordnetes Werk:	Enthalten in: Applied microbiology and biotechnology - Berlin : Springer, 1975, 99(2015), 15 vom: 24. Feb., Seite 6327-6337
Übergeordnetes Werk:	volume:99 ; year:2015 ; number:15 ; day:24 ; month:02 ; pages:6327-6337

Links:	Volltext

DOI / URN:	10.1007/s00253-015-6459-7

Katalog-ID:	SPR003001466

Internformat


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245	1	0	\|a Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
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520			\|a Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA.
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700	1		\|a Guo, Ning \|4 aut
700	1		\|a Zhang, Wei \|4 aut
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912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
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912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2070
912			\|a GBV_ILN_2086
912			\|a GBV_ILN_2093
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912			\|a GBV_ILN_2107
912			\|a GBV_ILN_2110
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allfields	10.1007/s00253-015-6459-7 doi (DE-627)SPR003001466 (SPR)s00253-015-6459-7-e DE-627 ger DE-627 rakwb eng Wang, Fang verfasserin aut Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2015 Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213 Yu, Jiyun aut Wang, Yu aut Jiang, Yunbo aut Guo, Ning aut Zhang, Wei aut Enthalten in Applied microbiology and biotechnology Berlin : Springer, 1975 99(2015), 15 vom: 24. Feb., Seite 6327-6337 (DE-627)265509564 (DE-600)1464336-4 1432-0614 nnns volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337 https://dx.doi.org/10.1007/s00253-015-6459-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2110 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 99 2015 15 24 02 6327-6337
spelling	10.1007/s00253-015-6459-7 doi (DE-627)SPR003001466 (SPR)s00253-015-6459-7-e DE-627 ger DE-627 rakwb eng Wang, Fang verfasserin aut Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2015 Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213 Yu, Jiyun aut Wang, Yu aut Jiang, Yunbo aut Guo, Ning aut Zhang, Wei aut Enthalten in Applied microbiology and biotechnology Berlin : Springer, 1975 99(2015), 15 vom: 24. Feb., Seite 6327-6337 (DE-627)265509564 (DE-600)1464336-4 1432-0614 nnns volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337 https://dx.doi.org/10.1007/s00253-015-6459-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2110 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 99 2015 15 24 02 6327-6337
allfields_unstemmed	10.1007/s00253-015-6459-7 doi (DE-627)SPR003001466 (SPR)s00253-015-6459-7-e DE-627 ger DE-627 rakwb eng Wang, Fang verfasserin aut Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2015 Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213 Yu, Jiyun aut Wang, Yu aut Jiang, Yunbo aut Guo, Ning aut Zhang, Wei aut Enthalten in Applied microbiology and biotechnology Berlin : Springer, 1975 99(2015), 15 vom: 24. Feb., Seite 6327-6337 (DE-627)265509564 (DE-600)1464336-4 1432-0614 nnns volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337 https://dx.doi.org/10.1007/s00253-015-6459-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2110 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 99 2015 15 24 02 6327-6337
allfieldsGer	10.1007/s00253-015-6459-7 doi (DE-627)SPR003001466 (SPR)s00253-015-6459-7-e DE-627 ger DE-627 rakwb eng Wang, Fang verfasserin aut Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2015 Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213 Yu, Jiyun aut Wang, Yu aut Jiang, Yunbo aut Guo, Ning aut Zhang, Wei aut Enthalten in Applied microbiology and biotechnology Berlin : Springer, 1975 99(2015), 15 vom: 24. Feb., Seite 6327-6337 (DE-627)265509564 (DE-600)1464336-4 1432-0614 nnns volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337 https://dx.doi.org/10.1007/s00253-015-6459-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2110 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 99 2015 15 24 02 6327-6337
allfieldsSound	10.1007/s00253-015-6459-7 doi (DE-627)SPR003001466 (SPR)s00253-015-6459-7-e DE-627 ger DE-627 rakwb eng Wang, Fang verfasserin aut Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2015 Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213 Yu, Jiyun aut Wang, Yu aut Jiang, Yunbo aut Guo, Ning aut Zhang, Wei aut Enthalten in Applied microbiology and biotechnology Berlin : Springer, 1975 99(2015), 15 vom: 24. Feb., Seite 6327-6337 (DE-627)265509564 (DE-600)1464336-4 1432-0614 nnns volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337 https://dx.doi.org/10.1007/s00253-015-6459-7 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2110 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2360 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 99 2015 15 24 02 6327-6337
language	English
source	Enthalten in Applied microbiology and biotechnology 99(2015), 15 vom: 24. Feb., Seite 6327-6337 volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337
sourceStr	Enthalten in Applied microbiology and biotechnology 99(2015), 15 vom: 24. Feb., Seite 6327-6337 volume:99 year:2015 number:15 day:24 month:02 pages:6327-6337
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Rheumatoid arthritis Combination therapy CTLA4-FasL TNFR-Fc
isfreeaccess_bool	false
container_title	Applied microbiology and biotechnology
authorswithroles_txt_mv	Wang, Fang @@aut@@ Yu, Jiyun @@aut@@ Wang, Yu @@aut@@ Jiang, Yunbo @@aut@@ Guo, Ning @@aut@@ Zhang, Wei @@aut@@
publishDateDaySort_date	2015-02-24T00:00:00Z
hierarchy_top_id	265509564
id	SPR003001466
language_de	englisch
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author	Wang, Fang
spellingShingle	Wang, Fang misc Rheumatoid arthritis misc Combination therapy misc CTLA4-FasL misc TNFR-Fc Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
authorStr	Wang, Fang
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topic_title	Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats Rheumatoid arthritis (dpeaa)DE-He213 Combination therapy (dpeaa)DE-He213 CTLA4-FasL (dpeaa)DE-He213 TNFR-Fc (dpeaa)DE-He213
topic	misc Rheumatoid arthritis misc Combination therapy misc CTLA4-FasL misc TNFR-Fc
topic_unstemmed	misc Rheumatoid arthritis misc Combination therapy misc CTLA4-FasL misc TNFR-Fc
topic_browse	misc Rheumatoid arthritis misc Combination therapy misc CTLA4-FasL misc TNFR-Fc
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title	Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
ctrlnum	(DE-627)SPR003001466 (SPR)s00253-015-6459-7-e
title_full	Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
author_sort	Wang, Fang
journal	Applied microbiology and biotechnology
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author_browse	Wang, Fang Yu, Jiyun Wang, Yu Jiang, Yunbo Guo, Ning Zhang, Wei
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author-letter	Wang, Fang
doi_str_mv	10.1007/s00253-015-6459-7
title_sort	combination therapy with tnfr-fc and ctla4-fasl using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
title_auth	Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
abstract	Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. © Springer-Verlag Berlin Heidelberg 2015
abstractGer	Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. © Springer-Verlag Berlin Heidelberg 2015
abstract_unstemmed	Abstract The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of key pathogenic factors an attractive therapeutic strategy. We have previously reported a novel recombinant adeno-associated virus (AAV) vector, AAV.TFCF, which mediates separate coexpression of TNFα antagonist TNFR-Fc and T cell antagonist CTLA4-FasL both in vitro and in vivo (the injected joints). The purpose of this study was to examine the efficacy of TNFR-Fc/CTLA4-FasL combination therapy mediated by AAV.TFCF in experimental model of RA. Adjuvant-induced arthritis (AIA) was induced in Lewis rats, and the recombinant AAV.TFCF was injected into rat ankle joints. AAV vector encoding CTLA4-FasL (AAV.CTFA) or TNFR-Fc (AAV.TRFC) was used as the monotherapy control, and an AAV vector mediating the expression of enhanced green fluorescent protein (AAV.EGFP) was used as the negative control. The combination treatment mediated by AAV.TFCF demonstrated a more effective suppression of AIA compared with those monotherapy controls, as reflected in the clinical and histological observations. The synergistic anti-inflammatory effect of TNFR-Fc combining with CTLA4-FasL was proved to be associated with the greater reductions of inflammatory CD4+ T cell infiltration and proinflammatory cytokine TNFα level in the arthritic joints. In addition, the combination therapy was found to be able to increase the frequency of CD4 + CD25 + FoxP3+ regulatory T cell population in rat draining lymph nodes and suppress splenic inflammatory responses. These results suggest that combination treatment with TNFR-Fc and CTLA4-FasL may achieve superior efficacy in suppressing RA, and using this novel recombinant AAV.TFCF to obtain the combined counteraction of both pathogenic T cells and the key proinflammatory cytokine TNFα may provide a more effective and desirable strategy for treatment of RA. © Springer-Verlag Berlin Heidelberg 2015
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container_issue	15
title_short	Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats
url	https://dx.doi.org/10.1007/s00253-015-6459-7
remote_bool	true
author2	Yu, Jiyun Wang, Yu Jiang, Yunbo Guo, Ning Zhang, Wei
author2Str	Yu, Jiyun Wang, Yu Jiang, Yunbo Guo, Ning Zhang, Wei
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doi_str	10.1007/s00253-015-6459-7
up_date	2024-07-03T16:38:53.586Z
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Combination therapy with TNFR-Fc and CTLA4-FasL using the recombinant adeno-associated virus potently suppresses adjuvant-induced arthritis in rats

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