Therapeutic antibodies and proteins can induce an immune response in patients leading to the development of anti-drug antibodies (ADAs). These potentially lead to reduced efficacy through rapid clearance or neutralisation of the drug or toxicity due to cross-reaction with proteins in the body. Although the potential for immunogenicity of therapeutic antibodies and proteins has been significantly reduced through the application of protein engineering technologies, clinical data shows that many biopharmaceuticals still induce an immune response in patients. It therefore remains a concern for companies developing new products and for the regulatory agencies asked to approve their use.
EpiScreen™ – Ex vivo assessment of immunogenicity
EpiScreen™ is an accurate and sensitive way to assess the potential immunogenicity of proteins and antibodies ex vivo by measuring CD4+ T cell responses, the primary drivers of memory-based immunogenicity. These technologies are used across the industry as a standard for preclinical immunogenicity testing. EpiScreen™ is offered in three assay formats.
The EpiScreen™ time course T cell assay is widely used to assess the potential immunogenicity of therapeutic antibodies and other proteins before they reach the clinic. Read more >>>
The EpiScreen™ DC:T cell assay is used to assess the potential immunogenicity of therapeutic antibodies or other proteins that directly modulate CD4+ T cell activation. Read more >>>
EpiScreen™ T cell epitope mapping identifies the precise number and location of T cell epitopes within an antibody or protein. These can then be eliminated by generating humanised antibodies or deimmunised proteins. Read more >>>
EpiScreen™ MAPPs detects and sequences naturally processed and presented peptides in the context of MHC Class II utilising highly powerful mass spectrometry. Read more >>>
In silico assessment of immunogenicity
iTope™ and T Cell Epitope Database (TCED™) are in silico tools to rapidly screen antibodies and proteins for potential immunogenicity. Combined, they provide a more accurate prediction of T cell epitopes than other in silico technologies that rely on MHC class II binding analysis alone.
Using TCED™ we can screen amino acid sequences from antibodies or proteins against known epitopes (or non-immunogenic sequences) derived from previous EpiScreen™ T cell epitope mapping studies enabling us to more effectively create humanised antibodies and deimmunised proteins. Read more >>>
Assessing the immunogenicity of sub-visible aggregates
The presence of aggregates in biotherapeutics can have a critical effect on the biological activity of the molecule as well as immunogenicity in vivo.
GreenLight can artificially stress proteins to induce the formation of sub-visible aggregates of different properties at quantities that may be present in clinical material (after storage and handling). The stressed antibodies are characterised with an orthogonal analytical approach and compared for their immunogenic potential in vitro.