Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease

Freitag, Tobias; Podojil, Joseph R.; Pearson, Ryan M.; Fokta, Frank J.; Sahl, Cecilia; Messing, Marcel; Andersson, Leif C.; Leskinen, Katarzyna; Saavalainen, Päivi; Hoover, Lisa I.; Huang, Kuo Chan; Phippard, Deborah; Maleki, Saeed; King, Nicholas J. C.; Shea, Lonnie D.; Miller, Stephen D.; Meri, Seppo; Getts, Daniel R.

doi:10.1053/j.gastro.2020.01.045

Cited by 105 publications

(79 citation statements)

References 37 publications

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“…For example, tolerogenic immune modifying NPs [TIMP GLIA] encapsulated with gliadin protein were administered to mice intravenously, resulting in the restoration of peripheral tolerance to gluten and protection from celiac disease. 13 The treatment significantly reduced the histopathological changes observed in the duodenum and reversed the effects of dietary gluten challenge when compared with the gluten positive control. 13 The nonobese diabetic mouse is a commonly used animal model to investigate T1D.…”

Section: Commonly Used Animal Models Of Immune Tolerancementioning

confidence: 91%

“…13 The treatment significantly reduced the histopathological changes observed in the duodenum and reversed the effects of dietary gluten challenge when compared with the gluten positive control. 13 The nonobese diabetic mouse is a commonly used animal model to investigate T1D. In this model, pathological autoimmune T cells mediate the damage of insulin-producing b cells in the pancreas.…”

Section: Commonly Used Animal Models Of Immune Tolerancementioning

confidence: 91%

“…No drug-related toxicity was noted in rodent species, mice and rats, which were used to conduct toxicokinetic and repeat-dose good laboratory practice toxicity studies to establish the no observed adverse effect level. 13 In phase 2 clinical trials, celiac disease subjects needed to be positive for HLA-DQ2 or HLA-DQ2/ DQ8 as inclusion criteria. In another example, first in human doses for an antigen-specific immunotherapy using a combination of 2 thyrotropin receptor peptides (termed ATX-GD-59) for the treatment of GD were determined based on safety margins from repeat-dose toxicity studies using only a rodent model.…”

Section: Toxicology Species Selection For Immune Tolerance Therapiesmentioning

confidence: 99%

“…23 For TIMP-GLIA, in vitro safety assays using human blood from healthy donors demonstrated that TIMP-GLIA did not cause complement activation, hemolysis, or platelet aggregation. 13 Using organoid technology might have future applications specific to investigating immune tolerance.…”

Section: Screening Considerations To Establish Immune Tolerance Safetymentioning

confidence: 99%

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Opinion on Immune Tolerance Therapeutic Development

Radi

Wynn

2020

Toxicol Pathol

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Immune tolerance is defined by an active state of immune system unresponsiveness to foreign and self-antigens. Loss of immune tolerance to self-antigens and the resulting overexpression of autoantibodies can lead to tissue injury and development of various autoimmune diseases. In drug development, the goal of newly emerging immune tolerance therapies is to treat autoimmune disorders by restoring the immunoregulatory capacity of the immune system. Development of immune tolerance targets is initiated with the establishment of pharmacological efficacy in relevant disease animal models, followed by their stepwise translation to humans. This review discusses the major challenges to developing tolerance inducing pharmaceutical drugs, including the selection of appropriate disease models to establish efficacy, adequate, and acceptable in vitro and in vivo safety assessments, relevant biomarkers of human safety and efficacy, and finally, some regulatory guidelines to successfully develop immune tolerance therapeutics. [Box: see text]

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Section: Commonly Used Animal Models Of Immune Tolerancementioning

confidence: 91%

Section: Commonly Used Animal Models Of Immune Tolerancementioning

confidence: 91%

Section: Toxicology Species Selection For Immune Tolerance Therapiesmentioning

confidence: 99%

Section: Screening Considerations To Establish Immune Tolerance Safetymentioning

confidence: 99%

See 2 more Smart Citations

Opinion on Immune Tolerance Therapeutic Development

Radi

Wynn

2020

Toxicol Pathol

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“…This research is hampered by the lack of good line research opportunity as the immune reaction to gluten is dependent on intact mucosal interaction. It is also hampered by lack of good animal (mouse) models for CD, although there are several mouse models for immune reaction to gluten (120,121). Recently, a mouse model was developed that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten (122).…”

Section: Development Of Other Non-dietary Treatment Optionsmentioning

confidence: 99%

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

et al. 2020

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Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis.

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Commonly Used Food Additives Are Nutritional Adjuvants in ASIA Syndrome

Lerner,

Benzvi

2024

Autoimmune Disorders

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Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease

Cited by 105 publications

References 37 publications

Opinion on Immune Tolerance Therapeutic Development

Opinion on Immune Tolerance Therapeutic Development

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

Commonly Used Food Additives Are Nutritional Adjuvants in ASIA Syndrome

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