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SIAT® In Silico Immunogenicity Assessment

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A variety of evidence indicates that many biotherapeutic drugs in clinical trials or the market are immunogenic to a variable extent. The immunogenicity should be assessed during drug development because it may compromise the safety and alter the pharmacokinetics of drugs in patients. Creative Biolabs has developed an efficient immunogenicity assessment platform, using our exclusive Sensitive Immunogenicity Assessment Technology® (SIAT®). SIAT® in silico immunogenicity assessment is based on modern bioinformatics techniques in combination with experimental approaches and can be applied to the prediction of the immunogenicity of biotherapeutic drug candidates including protein, enzyme, antibody, ADC, etc.

Antigen-presenting cells (APCs), typically dendritic cells (DCs), can take up antigen in a non-specific manner and cleave the antigen into peptides with a length less than 34 amino acid residues in the endosome. These residues, also known as T cell epitopes, are then presented by human leukocyte antigen (HLA, or major histocompatibility complex, MHC) class II molecules to helper-T (Th) cells that are able to recognize them through specific T cell receptors (TCRs). This recognition leads to the proliferation and differentiation of Th cells. As a result, activated Th cells stimulate certain types of B cells to produce antibodies. This specific stimulation is mediated by the capture of antigenic peptides by B cell receptors (BCRs) expressed on B cells and the presentation of these peptides by MHC II molecules to Th cells. Similarly, the activation of CD8+ T cells depends on the peptides presented by HLA class I molecules (MHC I).

Therefore, the immunogenicity of biotherapeutic drugs is critically dependent on the presence of T cell epitopes. Both HLA class I and class II molecules show a high degree of polymorphism and are divided into different subtypes. The existence of different HLA allotypes enables HLA molecules to bind a broad range of peptides while preserving some specificity. The binding affinity of HLA molecules and peptides with different amino acid sequence is different, resulting in the correlation between the concentration of the presented peptide and intensity of T cell activation signal. Thus, estimation of the binding affinity of peptide sequences in a biotherapeutic drug candidate provides valuable information for its potential immunogenicity.

SIAT® in silico immunogenicity assessment service uses a three-dimensional (3D) structure computational modeling method to predict the binding affinity of the MHC molecule/peptide complex. The results of this service provide valuable information for customers to make important decisions for strategic plans. Below is a brief description of our workflow of SIAT® in silico immunogenicity assessment service.


The binding pocket of HLA (yellow) and peptide (red). 
(Giguère et al. 2013) The binding pocket of HLA (yellow) and peptide (red).
(Giguère et al. 2013)

SIAT® in silico immunogenicity assessment service takes into consideration the polymorphism of HLA molecules in both individual and a population. Most HLA alleles in the targeted population can be covered. We are able to screen large numbers of potential T epitopes in the biotherapeutic drug candidates, and the accuracy of our method has been confirmed by comparing the predicted values with the experimentally measured results. Our service has been successfully used in the evaluation of therapeutic agents, especially therapeutic antibodies. SIAT® in silico immunogenicity assessment service is best suited for early discovery and exploring stage of biotherapeutic drugs, the results of which provide valuable information that leads you to go through the next stage of drug development with fewer blind spots.

Reference
Giguère, Sébastien, et al. "Learning a peptide-protein binding affinity predictor with kernel ridge regression." BMC bioinformatics 14.1 (2013): 1.

More SIAT® Immunogenicity Related Services at Creative Biolabs
In Silico Immunogenicity Assessment
In Vitro Class II HLA Binding Assay
Ex Vivo Immunogenicity Assessment
    DC-T Cell Proliferation Assay
    Antigen Presentation Assay
In Vivo Immunogenicity Assessment
Anti-drug Antibodies (ADA) Assays
De-immunization Service


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