The root cause of the body's immunogenicity is that its protein sequence is present on the surface of T cells, which can activate T cells, resulting in the body's continuous production of a large number of antibodies, thereby reducing the therapeutic effect of the drug.
De-immunization is a new technique to remove T cell epitopes by combining immunological and molecular biology techniques. After antibody de-immunization, it is usually possible to reduce the localization of T cells and have no effect on the affinity of antibody binding. Based on our unique and comprehensive platform, Creative Biolabs provides antibody sequencing to reduce immunogenicity and improve the therapeutic effect of the drug.
Successful recognition and removal of immunodominant CD4+ T cell epitopes can significantly reduce the incidence and severity of antibody drugs through immune ignorance. Based on the accumulation of knowledge to determine which T cell epitopes may have immunogenicity, we propose a method to reduce or remove immunogenicity.
This method uses antibody sequencing technology as a basis to determine the content and position of T cell epitopes, thereby guiding the de-immunization pathway of antibody drugs.
1. Using antibody sequencing to scan the primary structure of the protein, identify the main T cell epitopes, and search for the motifs containing anchored residues.
2. New peptides were synthesized by using the residues which are important for anchoring into major histocompatibility complex (MHC) groove, and the reactivity and immunogenicity of these modified peptide epitopes were tested.
3. Structure and homology analysis guide the targeting and substitution of key amino acids to maintain the required protein activity.
4. Site-directed mutations: target neutral residues that do not bind HLA but are also unlikely to significantly alter the folding and function of the modified protein.
5. Get de-immunization antibody drugs.
Fig.1 Identification, validation, and modification of epitopes. (Scott, 2010)
Creative Biolabs is a trusted antibody development service provider that has professional technical team to provide excellent antibody sequencing services. With extensive experience in antibody sequencing, we can employ advanced sequencing and immune technology to identify and remove T cell epitopes preferentially. If you are interested in our services, please contact us in time about more details and we are honored to serve you.
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