Discovery of Carbohydrate-Specific Antibodies from Non-Immune Libraries
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An antibody library is a diverse repertoire of antibody genes obtained from a donor's immunecells. These genes can be transformed into microorganisms and screened against specific antigens to uncover antibody sequences with affinity towards the target in question. Glycans, which can act as antigens, are cell-surface carbohydrates that contain glycosidic bonds and are used as biomarkers in research and diagnostic settings. Certain glycan expression is upregulated in cancerous cells and therefore is a valuable target for monoclonal antibody immunotherapeutics. However, one challenge to developing monoclonal antibody therapeutics is the time intensive and expensive immunization process. Foregoing this process would involve the usage of naïve libraries, which contain genes from non-immunized donors, and exploits the fact that a naïve library will contain a clone with a certain, albeit low, level of affinity for any given target. Naïve libraries were created from humanized mouse bone marrow and murine splenic cells. Yeast surface display techniques were used to screen these libraries against GD3 and polysialic acid (otherwise known as NeuNAcα2,8). Ultimately, desirable isolated antibody sequences from this process will be able to undergo further processing to become full-length monoclonal antibodies. The usage of this method could render naive antibody libraries as an efficient and valuable tool for antibody discovery, generating new sequences for the treatment of various diseases with upregulated expression of cell-surface GD3 and glycan structures containing polysialic acid.