The potential of this technique for clinical and diagnostic use became evident with the approval of the first therapeutic mAb 10 years later, Orthoclone OKT3 targeting the CD3 receptor present in T lymphocytes to control renal transplantation rejection. The fusion of B cells from immunized animals with myeloma cells originated hybrid cells producing unlimited quantities of antibodies with unique specificities. Generation of mAbs started with the discovery of the hybridoma technology by Köhler and Milstein in 1975. Every year, new mAbs are approved while a crescent number of other mAbs advance to the next phase of clinical study. Therapeutic mAbs are indicated to diverse clinical conditions such as treatment of cancers, immune-mediated disorders and infectious diseases, among others. The sale of therapeutic monoclonal antibodies (mAbs) is increasing yearly in relation to other class of biological products, and pharmaceutical/biotechnological companies are pursuing all opportunities to develop this product. The increasing applications of phage display technology will be highlighted in the antibody engineering area (affinity maturation, guided selection to obtain human antibodies) giving promising perspectives for the development of future therapeutics. This chapter contains an overview of discovery technologies, mainly display methods and antibody humanization methods for the selection of therapeutic humanized and human mAbs that appeared along the development of these technologies and thereafter. mAb humanization methods emerged as alternative for generating humanized variants of promising candidates obtained from non-human organism that could elicit an immune response.
Additionally to recombinant antibody selection, antibody engineering technologies were developed and explored to obtain desired characteristics of selected leading candidates such as high affinity, low immunogenicity, improved functionality, improved protein production, improved stability, and others.
The implantation of a robust platform of antibody discovery technologies allows reaching this goal. The development and improvement of strategies related to discovery technologies of monoclonal antibodies (mAbs) (phage display, yeast display, ribosome display, bacterial display, mammalian cell surface display, mRNA display, DNA display, transgenic animal, and human B-cell derived) opened perspectives for the screening and the selection of therapeutic antibodies for, theoretically, any target from any kind of organism.
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