Combination Immunotherapy for Type 1 Diabetes

Bone, Robert N.; Evans‐Molina, Carmella

doi:10.1007/s11892-017-0878-z

Cited by 28 publications

(14 citation statements)

References 125 publications

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“…Antigen-specific therapies have been pursued to downregulate diabetogenic autoimmune responses in T1D [27,28]. Therapies targeting antigen-specific T cells were deemed among the safest approaches and a variety of antigen delivery methods compatible with tolerance induction have been explored.…”

Section: Discussionmentioning

confidence: 99%

A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes

Postigo-Fernandez

Creusot

2019

Journal of Autoimmunity

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Type 1 diabetes (T1D) is caused by diabetogenic T cells that evaded tolerance mechanisms and react against multiple β-cell antigens. Antigen-specific therapy to reinstate tolerance (typically using a single β-cell antigen) has so far proved unsuccessful in T1D patients. Plasmid DNA (pDNA)-mediated expression of proinsulin has demonstrated transient protection in clinical trials, but long-lasting tolerance is yet to be achieved. We aimed to address whether pDNA delivery of multiple epitopes/mimotopes from several β-cell antigens efficiently presented to CD4 + and CD8 + T cells could also induce tolerance. This approach significantly delayed T1D development, while co-delivery of pDNA vectors expressing four full antigens protected more mice. Delivery of multiple epitopes resulted in a broad engagement of specific T cells, eliciting a response distinct from endogenous epitopes draining from islets. T-cell phenotypes also varied with antigen specificity. Unexpectedly, the repertoire of T cells reactive to the same epitope was highly polyclonal. Despite induction of some CD25 + Foxp3 + regulatory T cells, protection from disease did not persist after treatment discontinuation. These data demonstrate that epitope-based tolerogenic DNA vaccines constitute effective precision medicine tools to target a broad range of specific CD4 + and CD8 + diabetogenic T-cell populations for prevention or treatment of T1D.

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Section: Discussionmentioning

confidence: 99%

A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes

Postigo-Fernandez

Creusot

2019

Journal of Autoimmunity

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“…167–169 In response to growing evidence highlighting an active role for the β cell in disease pathogenesis, several ongoing trials are testing drugs that have successfully targeted β-cell stress responses in mouse models of diabetes. 170…”

Section: Disease-modifying Therapiesmentioning

confidence: 99%

Type 1 diabetes

2018

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Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

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“…Other trials using GAD65-based immunotherapy are ongoing, but once again, the results accumulated so far failed to show a significant efficacy in preventing the onset of type I diabetes or in restoring pancreatic islet β-cells function ( 17 , 18 ). Combination AITs could be a feasible option and a future research area, but more evidence is awaited ( 19 ). Multiple sclerosis is another complex immune-mediated disease with multiple identified autoantigens in which neurological lesions are unlikely to be completely healed after their onset.…”

Section: Antigen-based Immunotherapy and Its Application In Autoimmunmentioning

confidence: 99%

Vaccine Immunotherapy for Celiac Disease

et al. 2018

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Autoimmune and allergic disorders are highly prevalent conditions in which an altered or abnormal immune response is mounted against self- or environmental antigens, respectively. Antigen-based immunotherapy is a therapeutic option aimed at restoring the specific immune tolerance toward pathogenic antigens while leaving the rest of the immune system unaffected. This strategy proved efficacy especially in allergic diseases, including asthma, allergic rhinitis, and food allergies, but still has shortcomings for the treatment of autoimmune diseases. However, there are no available therapies, currently, in clinical practice for restoring the physiological tolerance that is typically lost in autoimmune diseases. In celiac disease, which is a common immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals, antigen-based immunotherapy could be a feasible option thanks to our deep understanding of the pathogenic mechanisms underpinning this condition. In fact, the immunodominant gluten epitopes are well-characterized and are recognized by pathogenic CD4+ T-cells that could be desensitized with immunotherapy. Moreover, the intestinal damage occurring in celiac disease (i.e., villous atrophy) is reversible upon gluten withdrawal. Only recently the results of a phase I trial of an intradermal, adjuvant-free, formulation of three specific gluten peptides (Nexvax2) showed a good safety profile, albeit its efficacy still needs to be demonstrated. More results are awaited, as they may radically change patients' quality of life that is constrained by the lifelong gluten-free diet and by the potential onset of life-threatening complications.

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Combination Immunotherapy for Type 1 Diabetes

Cited by 28 publications

References 125 publications

A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes

A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes

Type 1 diabetes

Vaccine Immunotherapy for Celiac Disease

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