Given the deleterious consequences of the immune response to anti-protein drugs, we need to assess and mitigate the risk of immunogenicity if we are to make the most of these powerful drugs. Creative BioMart provides solutions for inducing tolerance to therapeutic proteins using strategies and technologies that de-immunize biotherapeutic proteins, going on to assist pharmaceutical companies in developing powerful new drugs.

MHC-restricted T-cell Epitopes in Biotherapeutics

Epitope "deimmunization" of therapeutic proteins is an attractive approach to reduce their immunogenicity, which can be accomplished at the drug design stage without the need for later clinical intervention. The process of protein deimmunization can be divided into several steps: epitope prediction, epitope identification and epitope removal, so that the peptide epitope of the therapeutic protein is no longer present on the MHC molecule, i.e., the antigen-specific T-cell epitope is identified and removed, which can significantly reduce the incidence and severity of immunogenicity. Alternatively, reducing MHC affinity may also reduce the likelihood of effective pMHC-TCR formation leading to T-effector activation, proliferation, and signaling.

Fig.1 Deimmunized therapeutic proteins do not trigger immune response. (Zinsli L V, et al., 2021)

Strategies for epitope deimmunization show great potential for use in therapeutic protein products. By selecting alternative amino acids without altering the protein as a drug and thereby deleting these epitopes, the binding between antigen and T cells is disrupted through T-cell epitope deletion, thereby disrupting the immune response pathway to inhibit drug-resistant antibodies.

Our Deimmunization Solutions

Recognition, prediction and deletion of T-cell epitopes of biotherapeutic proteins can not only reduce their immunogenicity but also improve bioavailability.

Our Techniques and Tools

• Epitope identification techniques. The diversity of MHC brings a large number of various epitopes with huge and complex information that is difficult to handle. We offer machine learning techniques in the field of immunoinformatics for epitope prediction to predict and identify epitopes corresponding to different MHC molecules in a comprehensive manner.
• Immunoassay technology. Unique synthetic design of peptide-MHC complexes for immune molecules such as T cell proliferation or affinity assays to evaluate and measure T cell responses to relevant epitopes.

Creative BioMart's deimmunization solutions can help you manage the immunogenicity risk of therapeutic proteins, contact us for more immunogenicity assays.

References

• Zinsli L V, et al. "Deimmunization of protein therapeutics – Recent advances in experimental and computational epitope prediction and deletion." Computational and Structural Biotechnology Journal (2021),19,315-329.
• Pratt K P. "Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity" Antibodies (2018),7(2):19.