Assessment of the relative immunogenic potential of biologics using MHC Class II Associated Peptide Proteomics (MAPPs) and in silico/in vitro assays

One of the major hurdles in the development of protein therapeutics is the risk for unwanted immunogenicity which can lead to decreased efficacy and safety concerns. Other adverse immune-mediated reactions such as cytokine release syndrome can be a matter of major safety concern.

Although we have learned a lot on the immunogenicity of the first generations of mAbs over the past decades, it is still difficult to estimate the risks associated with modifications to the original mAbs or with novel protein therapeutic platforms.

Today, several tools are available to improve and accelerate therapeutic drug development in an early stage. A well balanced and rational development strategy can help to design less immunogenic drugs and reduce the number of clinical failures.

Often used as a first step is an in silico T cell epitope prediction algorithm such as NetMHCpan which can be used to assess and compare the immunogenic potential of the lead candidates and guide de immunization strategies.
Further monitoring of the immunogenic risk can be performed using in vitro T cell proliferation assays to determine and rank the immunogenic risk of the test proteins or identify specific regions of concern. Potential cytokine release-associated responses can be evaluated using in vitro whole blood or cellular assays.

Additionally, MHC Class II Associated Peptide Proteomics (MAPPs) is more and more used to allow a relative ranking of the immunogenic potential based on the bound peptides processed and presented by dendritic cells (DCs).
Finally, the compilation of the different datasets and translation of the results into a comprehensive risk management plan allows further de-risking of test candidates and the selection of the best candidates to move forward into humans.

Authors

Sofie Pattijn
Thibault Jonckheere
Jana Schockaert

Organisations

ImmunXperts SA, rue Auguste Piccard 48, 6041 Gosselies, Belgium

Presenting author

Sofie Pattijn, CTO, ImmunXperts SA
sofie.pattijn@immunxperts.com
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