Tolerogenic Immunomodulation by PEGylated Antigenic Peptides

Pfeil, Jennifer; Simonetti, Mario; Lauer, Uta; Volkmer, Rudolf; Thülen, Bianca von; Krähmer, Ralf; Leenders, Frank; Hoffmann, Ute

doi:10.3389/fimmu.2020.529035

Cited by 7 publications

(20 citation statements)

References 67 publications

(83 reference statements)

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“…In the DO11.10 adoptive transfer model, we demonstrated that vaccination with PEGylated peptides led to expansion and/or de novo induction of antigen-specific Tregs. 21 To analyze the role of antigen-specific Tregs in the prevention of EAE by pMOG-PEG20 pretreatment, tolerogenic vaccination was given 2 weeks prior to EAE induction and Tregs were depleted by injection of anti-CD25 antibody 7 days prior to EAE induction. As expected, Treg depletion significantly enhanced disease already in the PBS group.…”

Section: Resultsmentioning

confidence: 99%

“… 43 – 45 In the OVA-model, we observed that concomitant injection of lipopolysaccharide (LPS) completely prevented the induction of Tregs upon tolerogenic vaccination with pOVA-PEG20. 21 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…consisting of 20 ethylene units) if not otherwise mentioned, which was determined as the most effective carrier type in our preceding study. 21 …”

Section: Introductionmentioning

confidence: 99%

“…In a preceding study, we described that indeed, vaccination with PEG-coupled ovalbumin (OVA)-peptide in the DO11.10 experimental model results in a marked increase in Treg numbers and downregulation of effector T cells. 21 PEG is a synthetic polymer composed of repetitive ethylene oxide subunits, either in linear form, or as branched polymers. Numerous PEGylated biomolecules have already been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for human use as ingredients of foods, cosmetics and pharmaceuticals including topical, parenteral and nasal formulations.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides

Pfeil

Simonetti

Lauer

et al. 2021

Therapeutic Advances in Chronic Disease

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Background: Therapeutic treatment options for chronic autoimmune disorders such as multiple sclerosis (MS) rely largely on the use of non-specific immunosuppressive drugs, which are not able to cure the disease. Presently, approaches to induce antigen-specific tolerance as a therapeutic approach; for example, by peptide-based tolerogenic ‘inverse’ vaccines have regained great interest. We have previously shown that coupling of peptides to carriers can enhance their capacity to induce regulatory T cells in vivo. Method: In this present study, we investigated whether the tolerogenic potential of immunodominant myelin T-cell epitopes can be improved by conjugation to the synthetic carrier polyethylene glycol (PEG) in an experimental autoimmune encephalomyelitis (EAE) mouse model for chronic MS (MOG C57BL/6). Results: Preventive administration of the PEGylated antigenic peptide could strongly suppress the development of EAE, accompanied by reduced immune cell infiltration in the central nervous system (CNS). Depletion of regulatory T cells (Tregs) abrogated the protective effect indicating that Tregs play a crucial role in induction of antigen-specific tolerance in EAE. Treatment during the acute phase of disease was safe and did not induce immune activation. However, treatment at the peak of disease did not affect the disease course, suggesting that either induction of Tregs does not occur in the highly inflamed situation, or that the immune system is refractory to regulation in this condition. Conclusion: PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application for immunotherapy of overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…consisting of 20 ethylene units) if not otherwise mentioned, which was determined as the most effective carrier type in our preceding study. 21 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides

Pfeil

Simonetti

Lauer

et al. 2021

Therapeutic Advances in Chronic Disease

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Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

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Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.

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Regulation of Antigen‐Specific Immunotherapy with Nanomaterials

Ye,

Jia,

Ren

et al. 2023

Advanced NanoBiomed Research

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Nonspecific immunotherapies often induce general immune activation or suppression. Conversely, antigen‐specific immunotherapy, which refers to dampening or augmenting adaptive immunity against a disease‐specific antigen, increases T‐cell target specificity to pathological tissues, thereby reducing side effects on the rest of the immune system. Advances in engineering strategies for nanomaterials have enabled the feasible modulation of their physicochemical features to incorporate antigens and inherently interact with innate immune cells, which remarkably amplifies the orchestration of antigen‐specific immune responses against cancer and autoimmune diseases. From this contemporary perspective, the basic principles of antigen‐specific immunotherapy are briefly introduced and we elucidate how the latest nanoengineering paradigms regulate the functions of heterogeneous subsets of immune cells, such as antigen‐presenting cells, B cells, and regulatory or cytotoxic T cells, promoting antigen‐specific immunotherapy to treat autoimmune diseases and cancer. An outlook on prospects and remaining challenges have been discussed for, translating scientific discoveries of powerful nanomaterials into medical advances in antigen‐specific immunotherapy, thus offering new treatment modalities for patients with unmet needs.

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Tolerogenic Immunomodulation by PEGylated Antigenic Peptides

Cited by 7 publications

References 67 publications

Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides

Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

Regulation of Antigen‐Specific Immunotherapy with Nanomaterials

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