A Question of Tolerance—Antigen-Specific Immunotherapy for Type 1 Diabetes

Naranjo, Jeniffer D. Loaiza; Bergot, Anne‐Sophie; Buckle, Irina; Hamilton‐Williams, Emma E.

doi:10.1007/s11892-020-01363-3

Cited by 8 publications

(10 citation statements)

References 117 publications

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“…The identification of autoantigens driving T1D-specific B- and T-cell responses is rooted in human data, and further defined and evaluated in pre-clinical models [reviewed by ( 8 , 9 )]. However, pre-clinical studies evaluating the prognostic, diagnostic, and therapeutic relevance of T1D-associated autoantigens have often been conducted in the absence of a strong drug development context.…”

Section: Key Challengesmentioning

confidence: 99%

“…These therapies, possibly in combination with regenerative approaches, could restore glucose homeostasis by reducing the autoinflammatory pressure. ASI include various immunoregulatory formulations of proteins or peptides +/- adjuvants; plasmid-based therapies encoding multiple antigens +/- immune modulators; and antigen-presenting cell-based and engineered antigen-specific T-cell-based therapies [reviewed in ( 6 , 7 )] and some peptide, protein, and DNA-based ASI approaches have been tested in T1D [reviewed in ( 8 )]. ASIs require a high safety profile concomitant with exquisite target/organ specificity that does not compromise host responses to pathogens or elevate cancer risks.…”

Section: Introductionmentioning

confidence: 99%

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Overcoming Obstacles in the Development of Antigen-Specific Immunotherapies for Type 1 Diabetes

et al. 2021

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Antigen-specific immunotherapy (ASI) holds great promise for type 1 diabetes (T1D). Preclinical success for this approach has been demonstrated in vivo, however, clinical translation is still pending. Reasons explaining the slow progress to approve ASI are complex and span all stages of research and development, in both academic and industry environments. The basic four hurdles comprise a lack of translatability of pre-clinical research to human trials; an absence of robust prognostic and predictive biomarkers for therapeutic outcome; a need for a clear regulatory path addressing ASI modalities; and the limited acceptance to develop therapies intervening at the pre-symptomatic stages of disease. The core theme to address these challenges is collaboration—early, transparent, and engaged interactions between academic labs, pharmaceutical research and clinical development teams, advocacy groups, and regulatory agencies to drive a fundamental shift in how we think and treat T1D.

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Section: Key Challengesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overcoming Obstacles in the Development of Antigen-Specific Immunotherapies for Type 1 Diabetes

et al. 2021

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“…T1D is an autoimmune disease characterized by the destruction of the insulin‐producing β‐cells, where CD4 + and CD8 + effector T cells attack pancreatic β‐cell and damage their ability to produce insulin (INS) for controlling blood glucose levels. [ 20 ] T1D has been identified with a range of specific autoantigens including INS, proinsulin (PINS), glutamic acid decarboxylase (GAD65), heat shock protein 60 (HSP60), chromogranin A (ChgA), islet glucose‐6‐phosphatase catalytic subunit‐related protein (IGRP) and islet antigen‐2 (IA‐2). These autoantigens have been reported to play roles in the T1D model of non‐obese diabetes (NOD) mice and have been explored in clinical trials for tolerogenic therapies.…”

Section: Introductionmentioning

confidence: 99%

“…These autoantigens have been reported to play roles in the T1D model of non‐obese diabetes (NOD) mice and have been explored in clinical trials for tolerogenic therapies. [ 20,21 ]…”

Section: Introductionmentioning

confidence: 99%

Targeting Lymphoid Tissues to Promote Immune Tolerance

Chen

Sun

2021

Advanced Therapeutics

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The enormous research progress in autoimmune disorders makes the establishment of long-term clinical tolerance to autoantigens an accessible goal. This strategy endows lymphoid tissues with the tolerogenic ability to induce an unresponsive state toward autoantigens. Lymphoid tissues, as the crossroads, play integral roles in initiating immune activation and immunoregulation. Enormous efforts have driven the exploration of targeting delivery of tolerogenic agents to lymphoid tissues to reverse autoimmune disorders. Herein, the development of various tolerogenic therapies for autoimmune diseases are reviewed, the mechanisms of action from various lymphoid tissues to appropriate cell types by different administration routes are highlighted, and examples of lymphoid tissue-targeting strategies to improve tolerogenic therapy potency are discussed. First lymph nodes-targeting strategies for tolerance induction after interstitial or intra-lymph node (i.LN) injection are summarized, then liver and spleen-mediated tolerance after intravenous administration are described, and finally oral tolerance-based therapies are discussed. It is envisioned that tolerogenic therapy will emerge as a novel treatment for autoimmune diseases.

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“…Targeting is achieved by delivery and presentation of one or more of these antigens in a manner that results in deletion, regulation, anergy, and/or exhaustion of these autoreactive T cells. Selected autoantigens have been administered to patients in the form of proteins or peptides via parenteral, oral, or nasal routes, or in the form of protein-encoding DNA plasmids (DNA vaccines) ( 1 , 3 ). A wide variety of delivery vehicles have been developed and tested to funnel these antigens to specific cell types and/or anatomical locations, including various micro- and nanoparticles ( 4 ) and, more recently, soluble antigen arrays ( 5 ).…”

mentioning

confidence: 99%

Preclinical evaluation of a precision medicine approach to DNA vaccination in type 1 diabetes

Postigo-Fernandez

Firdessa-Fite

Creusot

2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance Antigen-specific immunotherapy may be improved by focusing on epitopes that are disease-relevant and known to be presented on an individual’s human leukocyte antigen (HLA) haplotype, while targeting T cells across multiple antigens and including specific neoepitopes that are not present in protein antigens and/or not produced beyond inflamed sites. Here, we provide proof of principle that such a strategy applied to tolerogenic DNA vaccination is effective in a preclinical model of autoimmune diabetes, paving the way for precision medicine using endogenously encoded epitopes. It takes a minimum number of regular treatments to achieve a level of tolerance and regulation that is needed to limit insulitis and provide sustained protection before treatment may be discontinued or reduced in frequency.

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A Question of Tolerance—Antigen-Specific Immunotherapy for Type 1 Diabetes

Cited by 8 publications

References 117 publications

Overcoming Obstacles in the Development of Antigen-Specific Immunotherapies for Type 1 Diabetes

Overcoming Obstacles in the Development of Antigen-Specific Immunotherapies for Type 1 Diabetes

Targeting Lymphoid Tissues to Promote Immune Tolerance

Preclinical evaluation of a precision medicine approach to DNA vaccination in type 1 diabetes

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