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Protein Deimmunisation Platform
Therapeutic proteins have the potential to elicit an unwanted immune response in patients. Clinical studies have shown that both human proteins (for example, EPO, IFNα and IFNβ) and non-human proteins (for example, staphylokinase and glucarpidase) can induce immune responses ranging from neutralizing antibodies to severe allergic reactions and even autoimmunity. Technologies employed to reduce the immunogenicity of proteins have not always proved effective or have led to a reduction in yield due to manufacturing issues.
T cell epitope identified and removed
Composite Protein™ technology improves upon the previous deimmunisation technologies through the incorporation of EpiScreen™ to more accurately identify and prioritise removal of T cell epitopes.
Through the use of EpiScreen™, T cell epitopes (the primary drivers of long-lived, memory based immunogenicity) are identified and ranked by magnitude and promiscuity. The T cell epitopes are then removed from the protein using proprietary in silico tools and new protein variants are designed.
Simultaneously, structure and homology analyses guide the targeting and substitution of key amino acids in order to retain the desired protein activity. Deimmunisation of the resulting Composite Protein™ is confirmed by the EpiScreen™ time course T cell assay.
Above: Immunoglbulin G-degrading enzyme from Streptococcus pyogenes (IdeS) has been identified as a potential treatment for IgG-mediated autoimmune diseases. It is a cysteine protease that specifically cleaves IgGs at the hinge region. Due to its inherent immunogenicity it required deimmunisation. In order to assess the potential immunogenicity of deimmunised IdeS in comparison to the wild type protein, CD4+ T cell responses were measured using an EpiScreen™ T-cell Time Course assay. CD4+ T cells were incubated with the samples and assessed for proliferation on days 5-8. T cell responses with a stimulation index ≥1.90 (indicated by red dotted line) that were significant (p <0.05) using an unpaired, two sample Student’s t-test were considered positive.
Composite Proteins™ can be produced using one or more non-human proteins as a reference.
Novel Composite Proteins™ can be generated from protein libraries and screened for new properties.
Composite Proteins™ can be generated in different formats including full-length proteins, protein fragments and fusion proteins.
Working with Abzena
Abzena’s services are tailored for each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of time. Our clients widely regard us as professional and attentive partners who deliver quality results.
To get more information, a quote or to schedule a teleconference please contact us.