Therapeutic Antibody Engineering and Selection Strategies.

Abstract

Antibody drugs became an increasingly important element of the therapeutic landscape. Their accomplishment has been driven by many unique properties, in particular by their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering.The expansion 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. Moreover, antibody engineering technologies were developed and explored to obtain chosen characteristics of selected leading candidates such as high affinity, low immunogenicity, improved functionality, improved protein production, improved stability, and others. 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. The increasing applications of these technologies 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.