Publications
These are the publications that have been authored by the EIP and its Working Groups.
T cell assays for non-clinical immunogenicity risk assessment: best practices recommended by the European Immunogenicity Platform
In vitro and in silico tools help drug developers reduce unwanted immunogenicity of biologics at the design stage. These include assays that examine different immune system processes leading to anti-drug antibody (ADA) or cytotoxic cellular response development, such as activation and peptide presentation by antigen-presenting cells, and CD4+ or CD8+ T cell activation, proliferation, and specificity. The CD4+ T cell response is critical for establishing persistent, class-switched and affinity-matured ADA that are more likely to have a clinical impact. Various formats of CD4+ T cell assays raise concerns about quality, variability, and validity across laboratories. Harmonization on some key aspects of these assays is achievable, although full standardization among industry and academic labs is unlikely. Thus, the European Immunogenicity Platform Non-Clinical Immunogenicity Risk Assessment working group (EIP-NCIRA) sought to establish good practices to maximize data confidence and ensure consistent data interpretation within each assay format. The recommendations presented regard key assay parameters that will better ensure consistency across the field including donor selection, cell and test article quality control, data analysis, as well as implementation of standard controls to further reduce analytical variability.
Frontiers in Immunology
12/01/2026
AUTHORS
Sophie Tourdot
Anette Christine Karle
Marc Rosenbaum
Chloé Ackaert
Pauline Le Vu
Michael Gutknecht
Maryam Ahmadi
Annelies W. Turksma
Timothy P. Hickling
KEYWORDS
immunogenicity
non-clinical risk assessment
T cell assays
best practices
de-immunization
mitigation
Dendritic cell maturation assay for non-clinical immunogenicity risk assessment: best practices recommended by the European Immunogenicity Platform
Early assessment and mitigation of non-clinical immunogenicity risk during early drug development is key for the development of safe and efficacious therapeutics. The dendritic cell (DC) maturation assay, one of the non-clinical immunogenicity risk assessment tools used in the drug development pipeline, investigates the ability of a test article to induce the maturation of immature monocyte-derived DCs, serving as an indicator of factors that may initiate an innate immune response and contribute to an adaptive immune response. These factors can be either intrinsic to the therapeutic’s mechanism of action and structure, or extrinsic from the final drug product, such as formulation components or contamination with host cell proteins or other impurities. Due to the nature of the assay, key parameters such as cell source, cell culture conditions, reagents, and assay-specific defined criteria for baseline response and positivity can differ amongst laboratories. In this manuscript, the specifics of this assay are discussed, key quality criteria for robustness are described, and the selection of appropriate controls to enable meaningful data interpretation are presented. The aim of conducting the DC maturation assay using best practices is to improve the assay to be fit-for-purpose and to facilitate comparability across projects and between laboratories.
Frontiers in Immunology
19/11/2025
AUTHORS
Chloé Ackaert
Bruno Gonzalez-Nolasco
Marc Rosenbaum
Mercedes Perez-Olivares
Michael Gutknecht
Axel Ducret
Anette Christine Karle
KEYWORDS
dendritic cells
maturation assay
immunogenicity
risk assessment
adjuvanticity
innate immunity
MAPPs assays for non-clinical immunogenicity risk assessment: best practices recommended by the European immunogenicity platform
The use of the MAPPs (Major histocompatibility complex Associated Peptide Proteomics) assay by pharmaceutical companies, service providers, and academic laboratories is rapidly increasing, attesting to its increasingly pivotal role in biotherapeutic drug candidate design, selection, and mechanistic investigations. Implementation of the MAPPs assay is labor-intensive, necessitating a high level of expertise. Differences observed in protocols established by laboratories may lead to considerable variability in data quality, limiting inter-laboratory comparisons. To address these challenges, the Non-Clinical Immunogenicity Risk Assessment working group (NCIRA) of the European Immunogenicity Platform (EIP) sought to provide comprehensive recommendations for establishing robust workflows that will ensure robust data and meaningful interpretation. Recognizing the improbability of the complete harmonization of protocols, we aimed to define and propose a set of best practices to maximize confidence in the data generated by laboratories. The work presented here reviews the pitfalls and limitations of the assay, proposes strategies to enhance assay sensitivity and robustness, and outlines approaches for data analysis, reporting, and interpretation. Additionally, the potential of the MAPPs assay for future applications such as clinical studies is discussed. By proposing measures and controls that support the development of high-quality MAPPs assays, we seek to improve their reproducibility and reliability for drug candidates’ nonclinical immunogenicity risk evaluation.
Frontiers in Immunology
10/10/2025
AUTHORS
A.C. Karle
K. L. Kopp
R.J. Seward
S. Tourdot
C. Ackaert
M. Gutknecht
E. Cloake
N. Smith
A. Ducret
KEYWORDS
MAPPs
immunogenicity
risk assessment
candidate ranking
harmonization strategy
Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform
Bringing safe and effective drugs to patients is of utmost importance for the pharmaceutical industry, with immunogenicity (IG) being a critical factor that influences both aspects. Biotherapeutics can elicit unwanted immune responses, potentially leading to (severe) safety implications, reduced patient benefits, and may result in termination of development. Therefore, understanding IG risks throughout drug development is essential for both drug developers and health agencies (HAs). The Immunogenicity Risk Assessment (IRA) facilitates the identification of IG risk factors and allows the establishment of effective mitigation and monitoring strategies. In this publication, the European Immunogenicity Platform (EIP) presents a comprehensive IRA framework aligned across pharmaceutical industry, emphasizing its significance in product development - from early de-risking to bioanalytical monitoring and mitigation measures during clinical trials. The EIP also provides an updated list of IG risks, offers distinct recommendations for assigning overall IG risk levels prior to the start of clinical development and highlights business considerations within this assessment.
Frontiers in Immunology
22/05/2025
AUTHORS
Joanna Grudzinska-Goebel
Karin Benstein
Karien Bloem
Kyra J. Cowan
Boris Gorovits
Maria Jadhav
Melody Janssen
Vibha Jawa
Andrea Kiessling
Daniel Kramer
Arno Kromminga
Marcel van der Linden
Susana Liu
Gregor P. Lotz
Linlin Luo
Mantas Malisauskas
Céline Marban-Doran
Daniel T. Mytych
Elisa Oquendo Cifuentes
Susanne Pippig
Sandra Ribes
Myrthe Rouwette
Weiping Shao
Sophie Tourdot
Karin Nana Weldingh
Veerle Snoeck
KEYWORDS
immunogenicity
immunogenicity risk assessment
biotherapeutics
immunogenicity mitigation
bioanalysis
anti-drug antibody
immunogenicity de-risking
immunogenicity monitoring