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Antibody Sequencing Provides a New Path for Antibody Therapy Research

Introduction Protein Sequencing Applications

Introduction of Therapeutic Antibody Drugs

Since the first clinical application approval in 1986, more than 100 therapeutic antibody drugs have entered clinical applications successively, and new antibody drugs are in the process of development and marketing every year.

With the development of technology, common technologies for antibody screening and discovery include phage display technology, transgenic mouse hybridoma technology, and single B cell technology. Phage display technology realizes the unification of protein or polypeptide genotype and phenotype, and the required antibody can be quickly screened by using existing gene fragments, but it is highly dependent on the library and cannot cope with the diversity and complexity of antibody types. The transgenic mouse hybridoma technology does not need to go through the traditional steps of expressing recombinant antibodies in molecular biology. It only needs to go through animal immunization, cell culture and cell fusion, mouse ascites preparation, and monoclonal antibody purification to complete the preparation of target antibodies. However, it still has the disadvantages of a complicated operation, high difficulty, and a low success rate. Single B cell technology has the advantages of high efficiency, complete human origin, and rich gene diversity. However, so far, the application potential of single B cell antibody production technology has not been realized. Single B cell antibody production technology is still limited by some practical conditions. Antibody discovery technology relying on protein de novo sequencing is simple and quick to operate, does not rely on any antibody library, and can handle a variety of antibody detections, so it has attracted more and more attention and favor from antibody drug discovery and developers.

Fig. 1 Screening of monoclonal antibodies by phage display technology. (Philipp Diebolder, 2017)Fig. 1 Screening of monoclonal antibodies by phage display technology. (Philipp Diebolder, 2017)

Fig. 2 Transgenic mouse hybridoma technology. (Aya Jakobovits, 2007)Fig. 2 Transgenic mouse hybridoma technology. (Aya Jakobovits, 2007)

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Protein Sequencing

The discovery of antibody sequences relies on gene and protein sequencing. Compared with gene sequencing, protein sequencing produces far fewer random matches, which is more conducive to the discovery of new antibody sequences. Among the protein sequencing methods, there are currently three commonly used methods: sequencing based on the Edman degradation method, peptide mapping analysis, and protein de novo sequencing. Among them, protein de novo sequencing has the advantage of being able to sequence the full length of any unknown protein without relying on any protein database, so it has become the preferred technology to obtain protein sequences.

Fig. 3 Three methods for monoclonal antibody sequencing. (Creative Biolabs)Fig. 3 Three methods for monoclonal antibody sequencing.

At present, the antibody sequencing technology developed based on protein de novo sequencing has gradually attracted the attention of researchers, including in basic research and antibody drug development. Creative Biolabs' antibody discovery platform can directly and efficiently discover high-affinity natural antibodies that play a role in the immune system, facilitate the production of recombinant antibodies, and provide a new way for antibody research and development.

Creative Biolabs' protein de novo sequencing technology breaks through the limitations of samples, can obtain protein sequences in complex samples, breaks the database dependence of traditional proteomics, and truly realizes de novo protein sequencing. Among them, Creative Biolabs has continuously optimized and upgraded the antibody sequencing technology based on its 20 years of technical accumulation and developed a simpler, faster, and more accurate antibody sequencing platform. The technical advantages of Creative Biolabs' protein de novo sequencing technology platform are as follows:

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Applications of Creative Biolabs' Antibody Discovery Platform

Based on the above characteristics and advantages, Creative Biolabs' antibody discovery service has been fully applied in many fields. These practical applications further highlight the professionalism and industry leadership of Creative Biolabs in antibody discovery.

New natural antibody discovery in tumors: Targeted therapy has been used in many clinical treatments of tumors, and the basis of targeted therapy is the discovery of various natural antibodies in tumors. Some studies have reported the use of natural antibodies in patients to treat tumors. This method overcomes the disadvantage of relying on existing protein sequences to develop targeted drugs and provides technical support for the development of new targeted drugs. The use of Creative Biolabs' antibody discovery platform can help researchers quickly identify and develop natural antibodies in the body and speed up the process of drug development.

Natural antibody production from the patient's own source: The preparation of antibody drugs using natural antibodies from patients has become an important research direction. In related studies, scientists have developed a technique that can specifically covalently connect the T cell redirection domain to any ready-made human immunoglobulin G or natural IgG isolated from serum to produce bispecific antibodies. This technology can use the antibodies of cancer patients to detect and treat their own cancer, so as to achieve accurate medical treatment and personalized treatment. Creative Biolabs's antibody discovery platform can sequence and identify new antibodies in organisms so as to quickly promote laboratory results to clinical practice and accelerate the development of new antibody drugs.

Research on therapeutic antibodies for autoimmune diseases: The pathogenesis of many autoimmune diseases is due to the production of pathogenic immunoglobulin G antibodies, which form immune complexes that can poison and attack normal cells and tissues and endanger human health. Through the antibody discovery platform of Creative Biolabs, we can quickly separate and detect antibodies in patients' blood without relying on the existing protein database, so as to develop targeted therapeutic antibodies and clinical treatment programs.

Identification of the immune response after intervention: Through the de novo antibody sequencing platform of Creative Biolabs, we can quickly evaluate the antibodies produced by the immune response.

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References
  1. Smith SL. Ten years of Orthoclone OKT3 (muromonab-CD3): a review. J Transpl Coord. 1996 Sep;6(3):109-19; quiz 120-1. doi: 10.7182/prtr.1.6.3.8145l3u185493182. PMID: 9188368.
  2. Diebolder, P., & Krawczyk, A. (2018). Detailed Protocols for the Selection of Antiviral Human Antibodies from Combinatorial Immune Phage Display Libraries. InTech. doi: 10.5772/intechopen.70139.
  3. Janin-Bussat MC, et al. Characterization of antibody drug conjugate positional isomers at cysteine residues by peptide mapping LC-MS analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Feb 15;981-982:9-13. doi: 10.1016/j.jchromb.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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