Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat
Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Jörns, Anne [verfasserIn] Arndt, Tanja [verfasserIn] Yamada, Shinichiro [verfasserIn] Ishikawa, Daichi [verfasserIn] Yoshimoto, Toshiaki [verfasserIn] Terbish, Taivankhuu [verfasserIn] Wedekind, Dirk [verfasserIn] van der Meide, Peter H. [verfasserIn] Lenzen, Sigurd [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2020. corrected publication 2021 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of molecular medicine - Berlin : Springer, 1922, 98(2020), 8 vom: 30. Juni, Seite 1125-1137 |
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| Übergeordnetes Werk: |
volume:98 ; year:2020 ; number:8 ; day:30 ; month:06 ; pages:1125-1137 |
| Links: |
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| DOI / URN: |
10.1007/s00109-020-01941-8 |
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| Katalog-ID: |
SPR040540316 |
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| 100 | 1 | |a Jörns, Anne |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a © The Author(s) 2020. corrected publication 2021 | ||
| 520 | |a Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. | ||
| 650 | 4 | |a Antibody combination therapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cytokines |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a LEW.1AR1- |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a rat |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Pancreatic beta cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Reversal |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Type 1 diabetes mellitus |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Arndt, Tanja |e verfasserin |4 aut | |
| 700 | 1 | |a Yamada, Shinichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ishikawa, Daichi |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimoto, Toshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Terbish, Taivankhuu |e verfasserin |4 aut | |
| 700 | 1 | |a Wedekind, Dirk |e verfasserin |4 aut | |
| 700 | 1 | |a van der Meide, Peter H. |e verfasserin |4 aut | |
| 700 | 1 | |a Lenzen, Sigurd |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of molecular medicine |d Berlin : Springer, 1922 |g 98(2020), 8 vom: 30. Juni, Seite 1125-1137 |w (DE-627)254630804 |w (DE-600)1462132-0 |x 1432-1440 |7 nnns |
| 773 | 1 | 8 | |g volume:98 |g year:2020 |g number:8 |g day:30 |g month:06 |g pages:1125-1137 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s00109-020-01941-8 |z kostenfrei |3 Volltext |
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10.1007/s00109-020-01941-8 doi (DE-627)SPR040540316 (SPR)s00109-020-01941-8-e DE-627 ger DE-627 rakwb eng 610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Jörns, Anne verfasserin aut Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020. corrected publication 2021 Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 Arndt, Tanja verfasserin aut Yamada, Shinichiro verfasserin aut Ishikawa, Daichi verfasserin aut Yoshimoto, Toshiaki verfasserin aut Terbish, Taivankhuu verfasserin aut Wedekind, Dirk verfasserin aut van der Meide, Peter H. verfasserin aut Lenzen, Sigurd verfasserin aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 98(2020), 8 vom: 30. Juni, Seite 1125-1137 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 https://dx.doi.org/10.1007/s00109-020-01941-8 kostenfrei 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_65 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_170 GBV_ILN_171 GBV_ILN_187 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_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_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 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_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.13 ASE 44.47 ASE 44.48 ASE AR 98 2020 8 30 06 1125-1137 |
| spelling |
10.1007/s00109-020-01941-8 doi (DE-627)SPR040540316 (SPR)s00109-020-01941-8-e DE-627 ger DE-627 rakwb eng 610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Jörns, Anne verfasserin aut Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020. corrected publication 2021 Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 Arndt, Tanja verfasserin aut Yamada, Shinichiro verfasserin aut Ishikawa, Daichi verfasserin aut Yoshimoto, Toshiaki verfasserin aut Terbish, Taivankhuu verfasserin aut Wedekind, Dirk verfasserin aut van der Meide, Peter H. verfasserin aut Lenzen, Sigurd verfasserin aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 98(2020), 8 vom: 30. Juni, Seite 1125-1137 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 https://dx.doi.org/10.1007/s00109-020-01941-8 kostenfrei 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_65 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_170 GBV_ILN_171 GBV_ILN_187 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_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_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 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_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.13 ASE 44.47 ASE 44.48 ASE AR 98 2020 8 30 06 1125-1137 |
| allfields_unstemmed |
10.1007/s00109-020-01941-8 doi (DE-627)SPR040540316 (SPR)s00109-020-01941-8-e DE-627 ger DE-627 rakwb eng 610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Jörns, Anne verfasserin aut Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020. corrected publication 2021 Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 Arndt, Tanja verfasserin aut Yamada, Shinichiro verfasserin aut Ishikawa, Daichi verfasserin aut Yoshimoto, Toshiaki verfasserin aut Terbish, Taivankhuu verfasserin aut Wedekind, Dirk verfasserin aut van der Meide, Peter H. verfasserin aut Lenzen, Sigurd verfasserin aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 98(2020), 8 vom: 30. Juni, Seite 1125-1137 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 https://dx.doi.org/10.1007/s00109-020-01941-8 kostenfrei 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_65 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_170 GBV_ILN_171 GBV_ILN_187 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_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_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 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_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.13 ASE 44.47 ASE 44.48 ASE AR 98 2020 8 30 06 1125-1137 |
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10.1007/s00109-020-01941-8 doi (DE-627)SPR040540316 (SPR)s00109-020-01941-8-e DE-627 ger DE-627 rakwb eng 610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Jörns, Anne verfasserin aut Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020. corrected publication 2021 Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 Arndt, Tanja verfasserin aut Yamada, Shinichiro verfasserin aut Ishikawa, Daichi verfasserin aut Yoshimoto, Toshiaki verfasserin aut Terbish, Taivankhuu verfasserin aut Wedekind, Dirk verfasserin aut van der Meide, Peter H. verfasserin aut Lenzen, Sigurd verfasserin aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 98(2020), 8 vom: 30. Juni, Seite 1125-1137 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 https://dx.doi.org/10.1007/s00109-020-01941-8 kostenfrei 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_65 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_170 GBV_ILN_171 GBV_ILN_187 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_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_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 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_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.13 ASE 44.47 ASE 44.48 ASE AR 98 2020 8 30 06 1125-1137 |
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10.1007/s00109-020-01941-8 doi (DE-627)SPR040540316 (SPR)s00109-020-01941-8-e DE-627 ger DE-627 rakwb eng 610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Jörns, Anne verfasserin aut Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020. corrected publication 2021 Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 Arndt, Tanja verfasserin aut Yamada, Shinichiro verfasserin aut Ishikawa, Daichi verfasserin aut Yoshimoto, Toshiaki verfasserin aut Terbish, Taivankhuu verfasserin aut Wedekind, Dirk verfasserin aut van der Meide, Peter H. verfasserin aut Lenzen, Sigurd verfasserin aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 98(2020), 8 vom: 30. Juni, Seite 1125-1137 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 https://dx.doi.org/10.1007/s00109-020-01941-8 kostenfrei 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_65 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_170 GBV_ILN_171 GBV_ILN_187 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_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_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 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_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.13 ASE 44.47 ASE 44.48 ASE AR 98 2020 8 30 06 1125-1137 |
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Enthalten in Journal of molecular medicine 98(2020), 8 vom: 30. Juni, Seite 1125-1137 volume:98 year:2020 number:8 day:30 month:06 pages:1125-1137 |
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Antibody combination therapy Cytokines LEW.1AR1- rat Pancreatic beta cells Reversal Type 1 diabetes mellitus |
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Journal of molecular medicine |
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Jörns, Anne @@aut@@ Arndt, Tanja @@aut@@ Yamada, Shinichiro @@aut@@ Ishikawa, Daichi @@aut@@ Yoshimoto, Toshiaki @@aut@@ Terbish, Taivankhuu @@aut@@ Wedekind, Dirk @@aut@@ van der Meide, Peter H. @@aut@@ Lenzen, Sigurd @@aut@@ |
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2020-06-30T00:00:00Z |
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Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. 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| author |
Jörns, Anne |
| spellingShingle |
Jörns, Anne ddc 610 bkl 42.13 bkl 44.47 bkl 44.48 misc Antibody combination therapy misc Cytokines misc LEW.1AR1- misc rat misc Pancreatic beta cells misc Reversal misc Type 1 diabetes mellitus Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
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610 - Medicine & health |
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1432-1440 |
| topic_title |
610 ASE 42.13 bkl 44.47 bkl 44.48 bkl Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat Antibody combination therapy (dpeaa)DE-He213 Cytokines (dpeaa)DE-He213 LEW.1AR1- (dpeaa)DE-He213 rat (dpeaa)DE-He213 Pancreatic beta cells (dpeaa)DE-He213 Reversal (dpeaa)DE-He213 Type 1 diabetes mellitus (dpeaa)DE-He213 |
| topic |
ddc 610 bkl 42.13 bkl 44.47 bkl 44.48 misc Antibody combination therapy misc Cytokines misc LEW.1AR1- misc rat misc Pancreatic beta cells misc Reversal misc Type 1 diabetes mellitus |
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ddc 610 bkl 42.13 bkl 44.47 bkl 44.48 misc Antibody combination therapy misc Cytokines misc LEW.1AR1- misc rat misc Pancreatic beta cells misc Reversal misc Type 1 diabetes mellitus |
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ddc 610 bkl 42.13 bkl 44.47 bkl 44.48 misc Antibody combination therapy misc Cytokines misc LEW.1AR1- misc rat misc Pancreatic beta cells misc Reversal misc Type 1 diabetes mellitus |
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Journal of molecular medicine |
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Journal of molecular medicine |
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| title |
Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
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(DE-627)SPR040540316 (SPR)s00109-020-01941-8-e |
| title_full |
Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
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Jörns, Anne |
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Journal of molecular medicine |
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Journal of molecular medicine |
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eng |
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600 - Technology |
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2020 |
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1125 |
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Jörns, Anne Arndt, Tanja Yamada, Shinichiro Ishikawa, Daichi Yoshimoto, Toshiaki Terbish, Taivankhuu Wedekind, Dirk van der Meide, Peter H. Lenzen, Sigurd |
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Jörns, Anne |
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10.1007/s00109-020-01941-8 |
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610 |
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verfasserin |
| title_sort |
translation of curative therapy concepts with t cell and cytokine antibody combinations for type 1 diabetes reversal in the iddm rat |
| title_auth |
Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
| abstract |
Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. © The Author(s) 2020. corrected publication 2021 |
| abstractGer |
Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. © The Author(s) 2020. corrected publication 2021 |
| abstract_unstemmed |
Abstract Proinflammatory cytokines released from the pancreatic islet immune cell infiltrate in type 1 diabetes (T1D) cause insulinopenia as a result of severe beta cell loss due to apoptosis. Diabetes prevention strategies targeting different cytokines with antibodies in combination with a T cell antibody, anti-TCR, have been assessed for therapy success in the LEW.1AR1-iddm (IDDM) rat, an animal model of human T1D. Immediately after diabetes manifestation, antibody combination therapies were initiated over 5 days with anti-TNF-α (tumour necrosis factor), anti-IL-1β (interleukin), or anti-IFN-γ (interferon) together with anti-TCR for the reversal of the diabetic metabolic state in the IDDM rat. Anti-TCR alone showed only a very limited therapy success with respect to a reduction of immune cell infiltration and beta cell mass regeneration. Anti-TCR combinations with anti-IL-1β or anti-IFN-γ were also not able to abolish the increased beta cell apoptosis rate and the activated immune cell infiltrate leading to a permanent beta cell loss. In contrast, all anti-TCR combinations with anti-TNF-α provided sustained therapy success over 60 to 360 days. The triple combination of anti-TCR with anti-TNF-α plus anti-IL-1β was most effective in regaining sustained normoglycaemia with an intact islet structure in a completely infiltration-free pancreas and with a normal beta cell mass. Besides the triple combination, the double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas. Key messages Anti-TCR is a cornerstone in combination therapy for autoimmune diabetes reversal.The combination of anti-TCR with anti-TNF-α was most effective in reversing islet immune cell infiltration.Anti-TCR combined with anti-IL-1β was not effective in this respect.The combination of anti-TCR with anti-TNF-α showed a sustained effect over 1 year. © The Author(s) 2020. corrected publication 2021 |
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Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat |
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https://dx.doi.org/10.1007/s00109-020-01941-8 |
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Arndt, Tanja Yamada, Shinichiro Ishikawa, Daichi Yoshimoto, Toshiaki Terbish, Taivankhuu Wedekind, Dirk van der Meide, Peter H. Lenzen, Sigurd |
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Arndt, Tanja Yamada, Shinichiro Ishikawa, Daichi Yoshimoto, Toshiaki Terbish, Taivankhuu Wedekind, Dirk van der Meide, Peter H. Lenzen, Sigurd |
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10.1007/s00109-020-01941-8 |
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| score |
7.4004498 |