Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Homann, Arne; Röckendorf, Niels; Kromminga, Arno; Frey, Andreas; Platts-Mills, Thomas A.E.; Jappe, Uta

doi:10.7150/thno.20654

Cited by 17 publications

(15 citation statements)

References 30 publications

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“…Assays of cross-sectional clinical samples can identify patterns associated with disease states, and longitudinal samples from the same subject can illustrate epitope drift during the course of treatment, e.g., immunotherapies following antibody detection. Such array analyses have proven valuable in vaccine studies [118,119] and in profiling of autoimmune disorders, infections and cancer [117], and they may also be applied to characterize ADAs [120]. Some promising recent developments include combination of peptide array data with results of phage display, protein structural information, B-cell epitope prediction algorithms, etc.…”

Section: Identifying and Modifying B-cell Epitopes In Biotherapeuticsmentioning

confidence: 99%

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Pratt

2018

Antibodies

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Abstract:The development of anti-drug antibodies (ADAs) following administration of biotherapeutics to patients is a vexing problem that is attracting increasing attention from pharmaceutical and biotechnology companies. This serious clinical problem is also spawning creative research into novel approaches to predict, avoid, and in some cases even reverse such deleterious immune responses. CD4 + T cells are essential players in the development of most ADAs, while memory B-cell and long-lived plasma cells amplify and maintain these responses. This review summarizes methods to predict and experimentally identify T-cell and B-cell epitopes in therapeutic proteins, with a particular focus on blood coagulation factor VIII (FVIII), whose immunogenicity is clinically significant and is the subject of intensive current research. Methods to phenotype ADA responses in humans are described, including T-cell stimulation assays, and both established and novel approaches to determine the titers, epitopes and isotypes of the ADAs themselves. Although rational protein engineering can reduce the immunogenicity of many biotherapeutics, complementary, novel approaches to induce specific tolerance, especially during initial exposures, are expected to play significant roles in future efforts to reduce or reverse these unwanted immune responses.

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Section: Identifying and Modifying B-cell Epitopes In Biotherapeuticsmentioning

confidence: 99%

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Pratt

2018

Antibodies

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“…We employed serum from peanut-allergic patients which had been shown beforehand to have a high specific IgE reactivity against the major peanut allergen Ara h 2 ( Table 2 ). Applying a microarray-based epitope mapping technique ( 27 , 28 ) we could identify several linear epitopes on Ara h 2 which are recognized by these IgE (data not shown). Based on these mapping experiments, we chose the 8mer R-D-P-Y-S-P-S-P as typical Ara h 2 epitope, which also encompasses two of the three immunodominant Ara h 2 epitopes previously described ( 37 ) and which reacted with all sera used by us (three different peanut-allergic donors, Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Total IgE content and specific IgE reactivity against the peanut allergen Ara h 2 were determined by ImmunoCAP assays (ThermoFisher Scientific/Phadia, Freiburg, Germany). Recognition of linear Ara h 2 epitopes by IgE from patient sera was resolved by in-house epitope mapping analysis as described before ( 27 – 30 ). Use of patient material for this study was approved by the ethics committee of the University of Luebeck (approval number 10-126).…”

Section: Methodsmentioning

confidence: 99%

IgE Epitope Profiling for Allergy Diagnosis and Therapy – Parallel Analysis of a Multitude of Potential Linear Epitopes Using a High Throughput Screening Platform

et al. 2020

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Krause et al. OBOC-Library Screening With IgE library by using IgE directed against those test-peptides at physiological concentrations (≤20 IU/ml of specific IgE), and disease-relevant bead-bound epitopes of the major peanut allergen Ara h 2 by screening with sera from peanut allergics. Thus, we established a platform with which one can find and validate new immunoglobulin targets using patient material which displays a largely unknown immunoglobulin repertoire.

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“…For instance, in the case of anti-TNF antibodies, ADA characterization showed that 90% of antiinfliximab antibodies are neutralizing and more than 97% of anti-adalimumab antibodies are also neutralizing (4). Studies exploring peptide sequences targeted by these ADAs identified B-cell epitopes notably on infliximab and adalimumab variable regions, close to the paratope (5,6). ADA development may lead to reduced BP serum concentrations due to the formation of immune complexes and a loss of efficacy (7) or adverse effects such as infusion reactions (8), cytokine release syndrome (9), or hypersensitivity reactions (2,10).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates

2020

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Patients treated with bioproducts (BPs) frequently develop anti-drug antibodies (ADAs) with potential neutralizing capacities leading to loss of clinical response or potential hypersensitivity reactions. Many factors can influence BP immunogenicity and could be related to the patient, the treatment, as well as to the product itself. Among these latter factors, it is now well accepted that BP aggregation is associated with an increased potential for immunogenicity, as aggregates seem to be correlated with ADA development. Moreover, the presence of high-affinity ADAs suggests a CD4 T-cell dependent adaptive immune response and therefore a pivotal role for antigenpresenting cells (APCs), such as dendritic cells (DCs). In this review, we address the in vitro methods developed to evaluate how monoclonal antibodies could trigger the immunization process by focusing on the role of aggregated antibodies in the establishment of this response. In particular, we will present the different cell-based assays that have been used to assess the potential of antibodies and their aggregates to modulate cellular mechanisms leading to activation and the biological parameters (cellular activation markers, proliferation and secreted molecules) that can be measured to evaluate the different cell activation stages and their consequences in the propagation of the immune response. Indeed, the use of such strategies could help evaluate the risk of BP immunogenicity and their role in mitigating this risk.

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Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera

Cited by 17 publications

References 30 publications

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

IgE Epitope Profiling for Allergy Diagnosis and Therapy – Parallel Analysis of a Multitude of Potential Linear Epitopes Using a High Throughput Screening Platform

Immunogenicity of Bioproducts: Cellular Models to Evaluate the Impact of Therapeutic Antibody Aggregates

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