SIAT^® De-immunization Service

The immunogenicity of biotherapeutic drugs is a significant problem during clinical applications. Many biotherapeutic drugs can develop unwanted immune responses in patients such as generation of anti-drug antibodies (ADAs), which results in treatment resistance and potentially life-threatening adverse effects. Although different techniques, including advanced technologies for the expression, purification and formulation of recombinant proteins, and the use of purely human or humanized proteins, have been developed to reduce the immunogenicity of biotherapeutic drugs, the problems remain to be completely eliminated. For instance, fully human antibodies, produced by phage display technology or transgenic mice, may still show degrees of immunogenicity.

Creative Biolabs offers SIAT® de-immunization service in conjunction with our SIAT® Immunogenicity Assessment Platform to assist our clients in reducing immunogenicity of biotherapeutic drug candidates. Our service has been widely used to remove the T cell epitopes from biotherapeutic drugs while preserving their therapeutic efficacy. The knowledge that backs up our de-immunization service is that helper-T cell response is necessary for the development of long-term humoral and cellular immunity.

We employ novel, creative and classic methods to decrease the immunogenicity of drug candidates through the combined use of immunological and molecular biology techniques. Our experienced scientists have established a systematic process for the development of a de-immunized antibody for production in various expression systems. With a wealth of experience and profound expertise, we will be of your great assistance for the advancement of your promising drug candidate into clinical trials. Below is a brief description the workflow of our de-immunization service for biotherapeutic drug candidates.

• Locate the T cell epitopes by our SIAT® immunogenicity assessment service.
• Construct a 3D model of the Fv domain of the antibody. The model will help to study the location of predicted T cell epitopes and to evaluate the effects of a substitution on the stability and binding affinity of the antibody. The 3D structure is modeled by homology to the most related structure.
• Make multiple sequence alignments of human and murine germline as a source of possible substitutions for T cell epitopes.
• Replace the T cell epitopes with a closest human germline sequence according to the multiple sequence alignments. If the possibilities of human germline are exhausted, continue with murine germline and then ad-hoc substitutions. All substitutions will be tested by the method in the next step.
• Test the compatibility of the substitutions with the 3D structure of the antibody. Check the affinity of the substitutions with HLA allotypes. The overlapping peptides should not be transformed into T cell epitopes. The substitutions should avoid inducing strain in the antibody scaffold.
• If all tests are passed, accept the substitution. Otherwise, new substitutions are evaluated and selected.

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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