Antigen-Specific Immunotherapies for Autoimmune Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 18184

Special Issue Editor


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Guest Editor
Aditx Therapeutics, Inc., 11161 Anderson Street, Suite 105-10014, Loma Linda, CA 92354, USA
Interests: immune regulation and tolerance; immunotherapies; antigen-specific immunotherapies; autoimmune disease; type 1 diabetes; antigen-specific biomarker assay; antigen-specific B cell therapy

Special Issue Information

Dear Colleagues,

This Special Issue, “Antigen-Specific Immunotherapies for Autoimmune Disease”, focuses on progress made in the discovery and development of safe and effective prevention and treatment strategies with immunotherapies that target antigenic structures in various autoimmune conditions. The discovery and development of such therapies is based on significant progress made during the past two decades in our understanding of immune tolerance and the role that autoreactive regulatory T and B lymphocytes play in maintaining such processes in autoimmunity. Importantly, this issue is intended to cross-pollinate therapeutic experiences among the different autoimmune disease fields such that successful induction of immune tolerance and immunoregulation in one autoimmune disease may be therapeutically translated to another.

We cordially invite authors to submit original research and review articles that advance our knowledge of (1) immune tolerance-inducing antigen-specific therapies used to prevent or treat autoimmune diseases, (2) antigen-specific biomarkers that guide the use of such therapies, and 3) combination of therapeutic approaches with immunomodulating agents that could improve the efficacy of antigen-specific immunotherapies in autoimmunity. Review articles that provide insight from clinical trial experiences are especially welcomed, as are reviews of antigen-specific B cell-targeted immunotherapies.

We hope you find this an exciting and unique opportunity to contribute to this fast-progressing field by publishing in the Biomedicines journal.

Dr. David G. Alleva
Guest Editor

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Keywords

  • immune regulation and tolerance
  • immunotherapies
  • antigen-specific immunotherapies
  • autoimmune disease
  • type 1 diabetes
  • antigen-specific biomarker assay
  • antigen-specific B cell therapy

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Published Papers (4 papers)

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Review

6 pages, 558 KiB  
Review
Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
by James E. DiLisio and Kathryn Haskins
Biomedicines 2021, 9(3), 240; https://doi.org/10.3390/biomedicines9030240 - 27 Feb 2021
Cited by 1 | Viewed by 2417
Abstract
Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we [...] Read more.
Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we review initial work exploring tolerance induction to a hybrid insulin peptide using a biodegradable, nanoparticle delivery system in non-obese diabetic (NOD) mice. The immune phenotype(s) and possible mechanism(s) behind antigen-specific tolerance induction were dissected with a disease transfer model using transgenic autoreactive mouse T cells. Treatment of NOD mice with peptide-coupled nanoparticles appeared to have a dual function in preventing diabetes onset, inducing anergy in effector T cells and enhancing the activity of regulatory T cells. Importantly, the ratio of these two cell types in the pancreas was pushed toward tolerance. Antigen-specific tolerance induction to hybrid insulin peptides has the translational potential to preserve islet β-cells in new-onset or at-risk patients and prevent recurrent autoimmunity in transplant patients. Full article
(This article belongs to the Special Issue Antigen-Specific Immunotherapies for Autoimmune Disease)
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13 pages, 1006 KiB  
Review
Non-Genetically Encoded Epitopes Are Relevant Targets in Autoimmune Diabetes
by Hai Nguyen, Perrin Guyer, Ruth A. Ettinger and Eddie A. James
Biomedicines 2021, 9(2), 202; https://doi.org/10.3390/biomedicines9020202 - 17 Feb 2021
Cited by 8 | Viewed by 2649
Abstract
Islet antigen reactive T cells play a key role in promoting beta cell destruction in type 1 diabetes (T1D). Self-reactive T cells are typically deleted through negative selection in the thymus or deviated to a regulatory phenotype. Nevertheless, those processes are imperfect such [...] Read more.
Islet antigen reactive T cells play a key role in promoting beta cell destruction in type 1 diabetes (T1D). Self-reactive T cells are typically deleted through negative selection in the thymus or deviated to a regulatory phenotype. Nevertheless, those processes are imperfect such that even healthy individuals have a reservoir of potentially autoreactive T cells. What remains less clear is how tolerance is lost to insulin and other beta cell specific antigens. Islet autoantibodies, the best predictor of disease risk, are known to recognize classical antigens such as proinsulin, GAD65, IA-2, and ZnT8. These antibodies are thought to be supported by the expansion of autoreactive CD4+ T cells that recognize these same antigenic targets. However, recent studies have identified new classes of non-genetically encoded epitopes that may reflect crucial gaps in central and peripheral tolerance. Notably, some of these specificities, including epitopes from enzymatically post-translationally modified antigens and hybrid insulin peptides, are present at relatively high frequencies in the peripheral blood of patients with T1D. We conclude that CD4+ T cells that recognize non-genetically encoded epitopes are likely to make an important contribution to the progression of islet autoimmunity in T1D. We further propose that these classes of neo-epitopes should be considered as possible targets for strategies to induce antigen specific tolerance. Full article
(This article belongs to the Special Issue Antigen-Specific Immunotherapies for Autoimmune Disease)
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10 pages, 524 KiB  
Review
Therapeutic Targeting of Autoreactive B Cells: Why, How, and When?
by Zachary C. Stensland, John C. Cambier and Mia J. Smith
Biomedicines 2021, 9(1), 83; https://doi.org/10.3390/biomedicines9010083 - 16 Jan 2021
Cited by 11 | Viewed by 6337
Abstract
B lymphocytes play critical roles in the development of autoimmunity, acting as autoantibody manufacturers, antigen-presenting cells, and producers of cytokines. Pan-B cell depletion has demonstrated efficacy in treatment of many autoimmune disorders, but carries with it an unfavorable safety profile due to global [...] Read more.
B lymphocytes play critical roles in the development of autoimmunity, acting as autoantibody manufacturers, antigen-presenting cells, and producers of cytokines. Pan-B cell depletion has demonstrated efficacy in treatment of many autoimmune disorders, but carries with it an unfavorable safety profile due to global immune suppression. Hence, attention has turned to the potential of autoantigen-specific B cell targeted therapies, which would deplete or silence pathogenic self-antigen-reactive cells while sparing B cells needed for immune defense. Here, we discuss the antigen-specific B cell-targeted approaches that are under development or are under consideration, that could be employed to allow for more precise therapy in the treatment of autoimmunity. Lastly, we discuss some of the challenges associated with antigen-specific B cell targeting that may impact their clinical applicability. Full article
(This article belongs to the Special Issue Antigen-Specific Immunotherapies for Autoimmune Disease)
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14 pages, 1172 KiB  
Review
B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes
by Jamie L. Felton, Holly Conway and Rachel H. Bonami
Biomedicines 2021, 9(1), 42; https://doi.org/10.3390/biomedicines9010042 - 6 Jan 2021
Cited by 6 | Viewed by 5854
Abstract
Islet autoantibodies are the primary biomarkers used to predict type 1 diabetes (T1D) disease risk. They signal immune tolerance breach by islet autoantigen-specific B lymphocytes. T-B lymphocyte interactions that lead to expansion of pathogenic T cells underlie T1D development. Promising strategies to broadly [...] Read more.
Islet autoantibodies are the primary biomarkers used to predict type 1 diabetes (T1D) disease risk. They signal immune tolerance breach by islet autoantigen-specific B lymphocytes. T-B lymphocyte interactions that lead to expansion of pathogenic T cells underlie T1D development. Promising strategies to broadly prevent this T-B crosstalk include T cell elimination (anti-CD3, teplizumab), B cell elimination (anti-CD20, rituximab), and disruption of T cell costimulation/activation (CTLA-4/Fc fusion, abatacept). However, global disruption or depletion of immune cell subsets is associated with significant risk, particularly in children. Therefore, antigen-specific therapy is an area of active investigation for T1D prevention. We provide an overview of strategies to eliminate antigen-specific B lymphocytes as a means to limit pathogenic T cell expansion to prevent beta cell attack in T1D. Such approaches could be used to prevent T1D in at-risk individuals. Patients with established T1D would also benefit from such targeted therapies if endogenous beta cell function can be recovered or islet transplant becomes clinically feasible for T1D treatment. Full article
(This article belongs to the Special Issue Antigen-Specific Immunotherapies for Autoimmune Disease)
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