Immunogenicity Assessment of Protein Drugs with pMHC

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Protein therapies account for a large portion of the pharmaceutical market, such as monoclonal antibodies and enzyme replacement therapies, which are capable of treating many clinical conditions, including autoimmune diseases, cancers, infectious diseases and genetic disorders, through highly specific regimens. However, immunogenicity has become a key factor limiting the therapeutic efficacy of protein drugs and affecting product safety, making immunogenicity risk assessment critical in drug development.

The immunogenicity of a protein drug candidate is an important issue that needs to be thoroughly evaluated during the drug development process. Creative BioMart offers immunogenicity assessment services to study drug-specific T-cell responses using pMHC complexes to ensure maximum efficacy and optimal safety of protein products.

Immunogenicity of Therapeutic Proteins

Fig.1 T cells recognize complexes of peptide
fragments of therapeutic proteins and MHC.
(Sinu P, et al., 2013)

The immunogenicity of therapeutic proteins is manifested by anti-drug antibodies (ADA) and hypersensitivity reactions. Antigen-presenting cells (APCs) are highly phagocytic and administered therapeutic proteins are phagocytosed and processed in the context of the MHC and presented to antigen-specific T cells. APCs stimulate T cells and promote B cell activation and differentiation into memory B cells and plasma cells, and when memory B cells are exposed to therapeutic proteins, plasma cells secrete anti-drug antibodies that recognize specific epitopes on proteins capable of APC MHC receptor presentation, resulting in immunogenicity.

Therefore, identification of all potential T cell epitopes in the drug protein content is a reasonable approach to assess immunogenicity by detecting epitopes presented in the identified proteins, characterizing the binding of these peptides to MHC in vitro, and measuring the proliferative response of T cells to the epitopes.

Use Our Assessment Solutions

We offer a variety of immunogenicity assessment protocols including computerized, in vitro, and animal models.

In vivo immunogenicity assessment. We use animal models for screening the immunogenicity of therapeutic proteins. Due to physiological differences, animal MHC receptors do not directly mimic human HLA receptors, so we offer transgenic mouse models and can also develop new models for each therapeutic protein of interest.
In vitro immunogenicity assessment. We offer services such as epitope mapping to identify immunogenic epitopes on proteins, assessment of MHC binding affinity and T-cell proliferation assays to evaluate the immunogenic potential of proteins and identify regions of immunogenicity.
In Silico Predictions. Proteomics-based technologies and existing databases of epitopes and prediction methods, such as IEDB, Epitome and SEDB, predict the binding between T cells and MHC by information from their recognized epitope data.

Our Advantages

Multiple assessment tools in vitro and in vivo can be selected or combined to improve the accuracy of immunogenicity risk assessment.
To inform drug development and assist in the development of strategies to mitigate the immunogenicity of therapeutic proteins.

Creative BioMart's solutions are straightforward to customize and our services can be tailored to your specific project requirements, providing a flexible and cost-effective solution during your drug development process. We are the right partner for you, contact us to discuss the immunogenicity risk management of your protein drug.

References

Sinu P, et al. "Evaluating the Immunogenicity of Protein Drugs by Applying In Vitro MHC Binding Data and the Immune Epitope Database and Analysis Resource." Journal of Immunology Research (2013), 2013.
Robert D and Sathy V B. "Immunogenicity of Protein Pharmaceuticals." Journal of Pharmaceutical Sciences (2019), 108(5): 1637-1654.

For research use only. Not for clinical use.