T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation–Updated Consensus and Review 2020

Evaluation of a 3D human artificial lymph node as test model for the assessment of immunogenicity of protein aggregates

(2019) Teresa Kraus et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Immunogenicity of Chimeric Antigen Receptor T-Cell Therapeutics

(2019) Boris Gorovits et al.   BIODRUGS

Phase 1 study of MK-4166, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) antibody, as monotherapy or with pembrolizumab (pembro) in patients (pts) with advanced solid tumors.

(2019) Kyriakos P. Papadopoulos et al.   JOURNAL OF CLINICAL ONCOLOGY

Modified DCs and MSCs with HPV E7 antigen and small Hsps: Which one is the most potent strategy for eradication of tumors?

(2019) Azam Bolhassani et al.   MOLECULAR IMMUNOLOGY

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics

(2019) Jasmine Davda et al.   Journal for ImmunoTherapy of Cancer

Combination of CTLA-4 and PD-1 blockers for treatment of cancer

(2019) Anand Rotte   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Risk stratification integrating genetic data for factor VIII inhibitor development in patients with severe hemophilia A

(2019) Delphine Bachelet et al.   PLoS One

TCPro: an In Silico Risk Assessment Tool for Biotherapeutic Protein Immunogenicity

(2019) Osman N. Yogurtcu et al.   AAPS Journal

Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry Enhances Cancer Epitope Prediction

(2019) Jennifer G. Abelin et al.   IMMUNITY

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

(2019) Antonino Cassotta et al.   NATURE MEDICINE

Hypersensitivity reactions to biologics used in rheumatology

(2019) Andrea Matucci et al.   Expert Review of Clinical Immunology

Predicting HLA class II antigen presentation through integrated deep learning

(2019) Binbin Chen et al.   NATURE BIOTECHNOLOGY

Robust prediction of HLA class II epitopes by deep motif deconvolution of immunopeptidomes

(2019) Julien Racle et al.   NATURE BIOTECHNOLOGY

Current In Vitro Assays for Prediction of T Cell Mediated Immunogenicity of Biotherapeutics and Manufacturing Impurities

(2019) Brian R. Duke et al.   Journal of Pharmaceutical Innovation

Therapeutic administration of Tregitope-Human Albumin Fusion with Insulin Peptides to promote Antigen-Specific Adaptive Tolerance Induction

(2019) Anne S. De Groot et al.   Scientific Reports

Safety, Tolerability, and Potential Clinical Activity of a Glucocorticoid-Induced TNF Receptor–Related Protein Agonist Alone or in Combination With Nivolumab for Patients With Advanced Solid Tumors

(2019) Kimberley M. Heinhuis et al.   JAMA Oncology

In silico and in vitro immunogenicity assessment of B-domain-modified recombinant factor VIII molecules

(2018) C. Bartholdy et al.   HAEMOPHILIA

Fine tuning subsets of CD4 + T cells by low-dosage of IL-2 and a new therapeutic strategy for autoimmune diseases

(2018) Zhen Zhao et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials

(2018) Dorothea Buck et al.   Multiple Sclerosis Journal

Identification of HLA-DRB1 association to adalimumab immunogenicity

(2018) Mohan Liu et al.   PLoS One

Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity

(2018) Ronit Mazor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials

(2018) Dorothea Buck et al.   Multiple Sclerosis Journal

The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation

(2018) Lidia Karabon et al.   Journal of Immunology Research

Emerging Issues in AAV-Mediated In Vivo Gene Therapy

(2018) Pasqualina Colella et al.   Molecular Therapy-Methods & Clinical Development

An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease

(2018) Zoheb B. Kazi et al.   GENETICS IN MEDICINE

Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines

(2018) Petar Scepanovic et al.   Genome Medicine

Oncolytic Viruses Partner With T-Cell Therapy for Solid Tumor Treatment

(2018) Amanda Rosewell Shaw et al.   Frontiers in Immunology

Regulatory T Cells and Their Association with Serum Markers and Symptoms in Systemic Lupus Erythematosus and Rheumatoid Arthritis

(2018) Vikas Kailashiya et al.   IMMUNOLOGICAL INVESTIGATIONS

Impact of gut microbiota on gut-distal autoimmunity: a focus on T cells

(2018) Maran L. Sprouse et al.   IMMUNOLOGY

The Immune Epitope Database (IEDB): 2018 update

(2018) Randi Vita et al.   NUCLEIC ACIDS RESEARCH

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

(2018) Amine Meliani et al.   Nature Communications

Regulation of the Germinal Center Response

(2018) Marisa Stebegg et al.   Frontiers in Immunology

Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity

(2017) Sandeep Kumar Dhanda et al.   IMMUNOLOGY

IL-10–Producing Infliximab-Specific T Cells Regulate the Antidrug T Cell Response in Exposed Patients

(2017) Alessandra Vultaggio et al.   JOURNAL OF IMMUNOLOGY

Immunogenicity assessment during the development of protein therapeutics

(2017) Amy S. Rosenberg et al.   JOURNAL OF PHARMACY AND PHARMACOLOGY

Genetic variations in toll-like receptors 7 and 8 modulate natural hepatitis C outcomes and liver disease progression

(2017) Fatima-Zohra Fakhir et al.   LIVER INTERNATIONAL

Oncolytic Virotherapy: A Contest between Apples and Oranges

(2017) Stephen J. Russell et al.   MOLECULAR THERAPY

ProteomicsDB

(2017) Tobias Schmidt et al.   NUCLEIC ACIDS RESEARCH

Post hoc assessment of the immunogenicity of bioengineered factor VIIa demonstrates the use of preclinical tools

(2017) Kasper Lamberth et al.   Science Translational Medicine

Hemophilia A inhibitor treatment: the promise of engineered T-cell therapy

(2017) Kalpana Parvathaneni et al.   Translational Research

The in vitro MIMIC® platform reflects age-associated changes in immunological responses after influenza vaccination

(2017) Allison Dauner et al.   VACCINE

Characterization of CD4 T Cell Epitopes of Infliximab and Rituximab Identified from Healthy Donors

(2017) Moustafa Hamze et al.   Frontiers in Immunology

Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell:PBMC assay

(2017) Heidi S. Schultz et al.   PLoS One

Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis

(2016) N. A. Kennedy et al.   ALIMENTARY PHARMACOLOGY & THERAPEUTICS

T cell response to FVIII

(2016) Marc Jacquemin et al.   CELLULAR IMMUNOLOGY

Tolerogenic nanoparticles to induce immunologic tolerance: Prevention and reversal of FVIII inhibitor formation

(2016) Ai-Hong Zhang et al.   CELLULAR IMMUNOLOGY

Circulating T cells to infliximab are detectable mainly in treated patients developing anti-drug antibodies and hypersensitivity reactions

(2016) A. Vultaggio et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Genetic variant of IL-10RA and susceptibility to rheumatoid arthritis in a Chinese population

(2016) Xiao-Ke Yang et al.   CLINICAL RHEUMATOLOGY

Flow cytometry: basic principles and applications

(2016) Aysun Adan et al.   CRITICAL REVIEWS IN BIOTECHNOLOGY

HIV-specific CD8+ T cells and HIV eradication

(2016) R. Brad Jones et al.   JOURNAL OF CLINICAL INVESTIGATION

CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

(2016) Cameron J. Turtle et al.   JOURNAL OF CLINICAL INVESTIGATION

Secukinumab, a novel anti–IL-17A antibody, shows low immunogenicity potential in human in vitro assays comparable to other marketed biotherapeutics with low clinical immunogenicity

(2016) Anette Karle et al.   mAbs

Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi

(2016) Yang Li et al.   NATURE MEDICINE

Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles

(2016) Takashi K. Kishimoto et al.   Nature Nanotechnology

Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics

(2016) Marisa K. Joubert et al.   PLoS One

Functional defects in CD4+ CD25high FoxP3+ regulatory cells in ankylosing spondylitis

(2016) Huifang Guo et al.   Scientific Reports

T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

(2015) Roberto Pacifici   Annals of the New York Academy of Sciences

Fine specificities of natural regulatory T cells after IVIG therapy in patients with Kawasaki disease

(2015) Jane C. Burns et al.   AUTOIMMUNITY

Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis

(2015) Sarah S. Thomas et al.   BIODRUGS

Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility

(2015) Meenu Wadhwa et al.   BIOLOGICALS

Elimination of murine and human T-cell epitopes in recombinant immunotoxin eliminates neutralizing and anti-drug antibodies in vivo

(2015) Ronit Mazor et al.   Cellular & Molecular Immunology

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

(2015) B. Rup et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody

(2015) L. Xue et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Immunogenicity to infliximab is associated with HLA-DRB1

(2015) Thomas Billiet et al.   GUT

Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A

(2015) Ronit Mazor et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Physical Characterization and In Vitro Biological Impact of Highly Aggregated Antibodies Separated into Size-Enriched Populations by Fluorescence-Activated Cell Sorting

(2015) Srivalli Telikepalli et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity

(2015) J. N. Mahlangu et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma

(2015) Aaron P Rapoport et al.   NATURE MEDICINE

Augmented Binary Substitution: Single-pass CDR germ-lining and stabilization of therapeutic antibodies

(2015) Sue Townsend et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IL2RA is associated with persistence of rheumatoid arthritis

(2015) H.W. van Steenbergen et al.   ARTHRITIS RESEARCH & THERAPY

Soluble T-Cell Receptors Produced in Human Cells for Targeted Delivery

(2015) Even Walseng et al.   PLoS One

Detection of Innate Immune Response Modulating Impurities in Therapeutic Proteins

(2015) Lydia Asrat Haile et al.   PLoS One

Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses

(2014) John S. Tsang et al.   CELL

Regulatory T cells in systemic lupus erythematosus

(2014) Kim Ohl et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

AAVrh.10 immunogenicity in mice and humans. Relevance of antibody cross-reactivity in human gene therapy

(2014) R Thwaite et al.   GENE THERAPY

Tregitope: Immunomodulation Powerhouse

(2014) Leslie Cousens et al.   HUMAN IMMUNOLOGY

Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool

(2014) J. Christoph Vahl et al.   IMMUNITY

Related impurities in peptide medicines

(2014) Matthias D’Hondt et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Continuous requirement for the TCR in regulatory T cell function

(2014) Andrew G Levine et al.   NATURE IMMUNOLOGY

The immune epitope database (IEDB) 3.0

(2014) Randi Vita et al.   NUCLEIC ACIDS RESEARCH

Human Leukocyte Antigen Genes and Interferon Beta Preparations Influence Risk of Developing Neutralizing Anti-Drug Antibodies in Multiple Sclerosis

(2014) Jenny Link et al.   PLoS One

Aggregation of Human Recombinant Monoclonal Antibodies Influences the Capacity of Dendritic Cells to Stimulate Adaptive T-Cell Responses In Vitro

(2014) Verena Rombach-Riegraf et al.   PLoS One

Recombinant immunotoxin for cancer treatment with low immunogenicity by identification and silencing of human T-cell epitopes

(2014) R. Mazor et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cell-Mediated Immunity to AAV Vectors, Evolving Concepts and Potential Solutions

(2014) Etiena Basner-Tschakarjan et al.   Frontiers in Immunology

A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies

(2013) Sandra Garcês et al.   ANNALS OF THE RHEUMATIC DISEASES

CD45RA–Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA–CD27+CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis

(2013) Fumichika Matsuki et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

T-cell dependent immunogenicity of protein therapeutics: Preclinical assessment and mitigation

(2013) Vibha Jawa et al.   CLINICAL IMMUNOLOGY

The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study

(2013) Balázs Szalay et al.   CLINICAL RHEUMATOLOGY

Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNFα biologics in rheumatic diseases

(2013) C. C. Mok et al.   CLINICAL RHEUMATOLOGY

The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab

(2013) Bella Ungar et al.   GUT

Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes

(2013) Daniel J Hui et al.   MOLECULAR THERAPY

The two-faced T cell epitope

(2013) Leonard Moise et al.   Human Vaccines & Immunotherapeutics

Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

(2013) Anne S De Groot et al.   Expert Review of Clinical Pharmacology

Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy

(2012) Jenny L. McGovern et al.   ARTHRITIS AND RHEUMATISM

The effect of autoimmune arthritis treatment strategies on regulatory T-cell dynamics

(2012) Gerdien Mijnheer et al.   CURRENT OPINION IN RHEUMATOLOGY

The Fate of Taspoglutide, a Weekly GLP-1 Receptor Agonist, Versus Twice-Daily Exenatide for Type 2 Diabetes: The T-emerge 2 trial

(2012) J. Rosenstock et al.   DIABETES CARE

Highly Aggregated Antibody Therapeutics Can Enhance thein VitroInnate and Late-stage T-cell Immune Responses

(2012) Marisa K. Joubert et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

In Vitro and In Vivo Studies of IgG-derived Treg Epitopes (Tregitopes): A Promising New Tool for Tolerance Induction and Treatment of Autoimmunity

(2012) Leslie P. Cousens et al.   JOURNAL OF CLINICAL IMMUNOLOGY

A predictive biomimetic model of cytokine release induced by TGN1412 and other therapeutic monoclonal antibodies

(2012) Vipra Dhir et al.   Journal of Immunotoxicology

Of [hamsters] and men

(2012) Andres H. Gutiérrez et al.   Human Vaccines & Immunotherapeutics

Taking immunogenicity assessment of therapeutic proteins to the next level

(2011) I.C. Büttel et al.   BIOLOGICALS

Effect of HLA DR epitope de-immunization of Factor VIII in vitro and in vivo

(2011) Leonard Moise et al.   CLINICAL IMMUNOLOGY

Molecular Mimicry as a Mechanism of Autoimmune Disease

(2011) Matthew F. Cusick et al.   CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY

T cell-independent B cell memory

(2011) Thierry Defrance et al.   CURRENT OPINION IN IMMUNOLOGY

Identification of genome-derived vaccine candidates conserved between human and mouse-adapted strains ofH. pylori

(2011) Leonard Moise et al.   Human vaccines & immunotherapeutics

Classification and Characterization of Therapeutic Antibody Aggregates

(2011) Marisa K. Joubert et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Differential effect of drug interference in immunogenicity assays

(2011) Margreet H. Hart et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Overcoming immunogenicity associated with the use of biopharmaceuticals

(2011) Michael G Tovey et al.   Expert Review of Clinical Pharmacology

Prediction of Immunogenicity of Therapeutic Proteins

(2010) Christine J. Bryson et al.   BIODRUGS

Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells

(2010) C. H. J. Lamers et al.   BLOOD

Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics

(2010) Danika Wullner et al.   CLINICAL IMMUNOLOGY

Evidence for Molecular Mimicry between Human T Cell Epitopes in Rotavirus and Pancreatic Islet Autoantigens

(2010) Margo C. Honeyman et al.   JOURNAL OF IMMUNOLOGY

On the Role of Aggregates in the Immunogenicity of Recombinant Human Interferon Beta in Patients with Multiple Sclerosis

(2010) Miranda M.C. van Beers et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

The immunogenicity of humanized and fully human antibodies

(2010) Fiona A. Harding et al.   mAbs

Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins

(2010) Darius Ghaderi et al.   NATURE BIOTECHNOLOGY

Control systems and decision making for antibody production

(2010) Christopher C Goodnow et al.   NATURE IMMUNOLOGY

Trace Levels of Innate Immune Response Modulating Impurities (IIRMIs) Synergize to Break Tolerance to Therapeutic Proteins

(2010) Daniela Verthelyi et al.   PLoS One

Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics

(2009) Anne S. De Groot et al.   CLINICAL IMMUNOLOGY

Evaluation of the Immuno-Stimulatory Potential of Stopper Extractables and Leachables by Using Dendritic Cells as Readout

(2009) Robert Mueller et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Quality by design for biopharmaceuticals

(2009) Anurag S Rathore et al.   NATURE BIOTECHNOLOGY

Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes"

(2008) A. S. De Groot et al.   BLOOD

The effects of IL-6 on CD4 T cell responses

(2008) Oliver Dienz et al.   CLINICAL IMMUNOLOGY

Prediction of immunogenicity: in silico paradigms, ex vivo and in vivo correlates

(2008) A DEGROOT et al.   CURRENT OPINION IN PHARMACOLOGY

Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins

(2008) Alain Beck et al.   CURRENT PHARMACEUTICAL BIOTECHNOLOGY

Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products

(2008) Eugen Koren et al.   JOURNAL OF IMMUNOLOGICAL METHODS

Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products

(2008) Gopi Shankar et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose

(2008) Christine H. Chung et al.   NEW ENGLAND JOURNAL OF MEDICINE

Epoetin-associated pure red cell aplasia: past, present, and future considerations

(2008) June M. McKoy et al.   TRANSFUSION

New Approaches to Prediction of Immune Responses to Therapeutic Proteins during Preclinical Development

(2008) Laura C A Perry et al.   Drugs in research & development