The immunogenicity of biotherapeutic drugs is a significant problem during clinical applications. Many biotherapeutic drugs can develop unwanted immune responses in patients such as the 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.
One of the main drivers of immunogenicity is the presence of human T cell epitopes in the protein sequence, which can activate helper T cells, thus continuously producing antibodies and neutralizing therapeutic effects. De-immunization is a new technology combining immunology and molecular biology to locate and remove T cell epitopes. Creative Biolabs offers a number of de-immunization services to assist our clients in reducing the 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.
Fig.1 Recognition and binding of antibody versus T cell epitopes occur via separate molecular mechanisms. (Griswold, 2016)
We employ novel, innovative and classic methods to reduce the immunogenicity of candidate antibody drugs by combining immunology and molecular biology techniques. In the case of antibody de-immunization, the mutation of the T cell epitope can be introduced without significantly reducing the binding affinity of the antibody. In general, "de-immunized" antibodies are produced by the expression of human constant regions and genes encoding these antibodies in mammalian cells. At present, our experienced scientists have established a systematic process to develop an immune antibody produced in various expression systems. With a wealth of experience and profound expertise, we will be of great assistance for the advancement of your promising drug candidate into clinical trials.
In addition to antibody drugs, therapeutic peptides and proteins are powerful next-generation drugs that can effectively treat a variety of devastating diseases, but the development and use of biotherapeutics entail unique challenges and risks. In particular, protein drugs are monitored by the immune system in the human body and the following anti-drug immune response will cause a wide range of problems, including pharmacokinetic changes, drug efficacy loss, and even life-threatening complications. Therefore, various methods have been taken to reduce or eliminate the immunogenicity of these drugs. Based on the detailed understanding of the cellular and molecular mechanisms underlying the anti-drug immune response, our RDIT® platform can be used to "delete" protein epitopes to enable the strategy of protein immunity.
Creative Biolabs offers comprehensive and professional technology for your drug de-immunization needs. We are honored to provide you with a customized schedule to help you with your research. If you are interested in our RDIT® de-immunization service, please contact us for more information.