Antigen-based immunotherapy for autoimmune disease: current status

Hirsch, Darren Lowell; Ponda, Punita

doi:10.2147/itt.s49656

Cited by 15 publications

(13 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that peptides used in combination can be more effective than individual sequences in preventing or reversing allo- or auto-antibody production. 32,34,42,43 Peptides 2 (aa6-20) and 82 (aa711-725) were selected to be tested in combination here, since epitopes they contain were previously identified as the most immunodominant, 7 capable of eliciting Th responses in 65% of ITP patients tested, and they had also each demonstrated some, albeit variable, inhibition of antibody generation in the individual peptide experiments. It was determined whether prior treatment with an equimolar mixture of peptides 2 (aa6-20) and 82 (aa711-725) prevented induction of the antibody response to immunization with purified GPIIb/IIIa.…”

Section: Resultsmentioning

confidence: 99%

“…23,24 In contrast to previous untargeted approaches, antigen-specific immunotherapy offers the prospect of rebalancing pathogenic CD4 + Th and Treg responses, without compromising the rest of the immune system. 28–32 Precedents in models of other immune-mediated diseases demonstrate that this can be achieved by appropriate administration of short, synthetic peptides containing CD4 + T-cell epitopes from the respective target antigens, with peptide products being tested in clinical trials for the treatment of a number of conditions, including type I diabetes, multiple sclerosis and rheumatoid arthritis. 28–32 The approach induces immune regulation, which, in addition to suppressing inflammatory T-cell responses, also has the potential to inhibit helper-dependent antibody production, as demonstrated by the success of peptide therapy in blocking IgG responses to the RhD blood group protein in a humanized murine model.…”

Section: Introductionmentioning

confidence: 99%

“…28–32 Precedents in models of other immune-mediated diseases demonstrate that this can be achieved by appropriate administration of short, synthetic peptides containing CD4 + T-cell epitopes from the respective target antigens, with peptide products being tested in clinical trials for the treatment of a number of conditions, including type I diabetes, multiple sclerosis and rheumatoid arthritis. 28–32 The approach induces immune regulation, which, in addition to suppressing inflammatory T-cell responses, also has the potential to inhibit helper-dependent antibody production, as demonstrated by the success of peptide therapy in blocking IgG responses to the RhD blood group protein in a humanized murine model. 33,34 Once peptides that span major T-cell epitopes have been mapped, key requirements for effective immunotherapy include delivery of these sequences in soluble form, in the absence of any adjuvant material.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Combination peptide immunotherapy suppresses antibody and helper T-cell responses to the major human platelet autoantigen glycoprotein IIb/IIIa in HLA-transgenic mice

Hall¹,

Lennon²,

Hall³

et al. 2018

Haematologica

View full text Add to dashboard Cite

Platelet destruction in immune thrombocytopenia is caused by autoreactive antibody and T-cell responses, most commonly directed against platelet glycoprotein IIb/IIIa. Loss of self-tolerance in the disease is also associated with deficient activity of regulatory T cells. Having previously mapped seven major epitopes on platelet glycoprotein IIIa that are recognized by helper T cells from patients with immune thrombocytopenia, the aim was to test whether peptide therapy with any of these sequences, alone or in combination, could inhibit responses to the antigen in humanized mice expressing HLA-DR15. None of the individual peptides, delivered by a putative tolerogenic regimen, consistently suppressed the antibody response to subsequent immunization with human platelet glycoprotein IIb/IIIa. However, the combination of glycoprotein IIIa peptides aa6-20 and aa711-725, which contain the predominant helper epitopes in patients and elicited the strongest trends to suppress when used individually, did abrogate this response. The peptide combination also blunted, but did not reverse, the ongoing antibody response when given after immunization. Suppression of antibody was associated with reduced splenocyte T-cell responsiveness to the antigen, and with the induction of a regulatory T-cell population that is more responsive to the peptides than to purified platelet glycoprotein IIb/IIIa. Overall, these data demonstrate that combinations of peptides containing helper epitopes, such as platelet glycoprotein IIIa aa6-20 and aa711-725, can promote in vivo suppression of responses to the major antigen implicated in immune thrombocytopenia. The approach offers a promising therapeutic option to boost T-cell regulation, which should be taken forward to clinical trials.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combination peptide immunotherapy suppresses antibody and helper T-cell responses to the major human platelet autoantigen glycoprotein IIb/IIIa in HLA-transgenic mice

Hall¹,

Lennon²,

Hall³

et al. 2018

Haematologica

View full text Add to dashboard Cite

show abstract

“…Despite a few promising results of early phases clinical trials in humans, the use of AIT for autoimmune diseases has not yet been brought into practice ( 13 ). This could be partially explained by the fact that by the time an autoimmune disease is diagnosed, tissue damage may have already occurred or become irreversible, as in the case of type I diabetes.…”

Section: Antigen-based Immunotherapy and Its Application In Autoimmunmentioning

confidence: 99%

Vaccine Immunotherapy for Celiac Disease

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

“…and RA as well as phase I studies in humans [213]. Finally, tDCs can be used as a new therapeutic strategy to reestablish immune tolerance or to prevent ADs [209,214].…”

Section: Immune Tolerance Induction As a Therapy For Autoimmune Diseasesmentioning

confidence: 99%

Generation of a novel mouse model for the study of autoimmune liver disease overlap syndrome

Fuchs¹,

Bayer²,

Manns³

et al. 2018

Journal of Hepatology

View full text Add to dashboard Cite

Antigen-based immunotherapy for autoimmune disease: current status

Cited by 15 publications

References 83 publications

Combination peptide immunotherapy suppresses antibody and helper T-cell responses to the major human platelet autoantigen glycoprotein IIb/IIIa in HLA-transgenic mice

Combination peptide immunotherapy suppresses antibody and helper T-cell responses to the major human platelet autoantigen glycoprotein IIb/IIIa in HLA-transgenic mice

Vaccine Immunotherapy for Celiac Disease

Generation of a novel mouse model for the study of autoimmune liver disease overlap syndrome

Contact Info

Product

Resources

About