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Immunogenicity testing for advanced therapy medicinal products

We carried out a study to review the state-of-the-art of advanced non-animal models in use for immunogenicity testing in advanced therapy medicinal products (ATMPs).

Advanced therapy medicinal products (ATMPs) are innovative therapies expected to reshape our approach towards several pathologies.

Immunogenicity testing is an important step in the development of these therapies since it aims to predict an adverse immune response of a patient prior to receiving a particular treatment.

Results from immunogenicity testing carried out using animal models might be misleading because of fundamental biological differences between the immune system of different species.

This can result in poor translation of pre-clinical findings into subsequent clinical phases, for example in deciding on the right dose that is both safe and efficacious for the patient.

The study

We analysed the scientific literature published from January 2014 to March 2019 and selected 88 peer-reviewed articles that used advanced non-animal models for testing immunogenicity of ATMPs.

The outcome of the study comprises:

  • Knowledge base

It contains detailed descriptions of 88 non-animal models being used for testing immunogenicity in ATMPs. It is easily downloadable as a spreadsheet file from the EURL ECVAM collection in the JRC Data Catalogue.

  • Technical report

A technical report that provides an in-depth analysis of the models identified and of the review methodology used.

  • Executive summary

We also created an executive summary to give an overview of the study and the main results.

Key findings

  • The majority of the advanced non-animal models have been used to test cell therapy products.
  • A great number of non-animal approaches used to test the immunogenicity of ATMPs were based on in vitro methods that mainly use cells and tissues cultured in the laboratory.
  • In contrast, it was found that computational and mathematical modelling (in silico methods) were less commonly used.


Notwithstanding the high investments in this field, the use of non-animal models is still rather uncommon to test the immunogenicity of ATMPs, and the publication trend has remained rather constant over the observed period.

This study highlighted that there is certainly room for improvement in several areas.

These include: achieving a more reliable and scalable supply of immune cells, commonly based on voluntary donors; increasing the number of samples that can be tested in an immunogenicity experiment; and implementing more advanced measurement technologies such as ’omics to generate more information from a test.

More innovative approaches could also be pursued through the incorporation of new technologies for high-throughput and high-content analysis. In addition, in silico models of the immune system should be definitely exploited further.