Chapters authored
Display Technologies for the Selection of Monoclonal Antibodies for Clinical Use
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. The implantation of a robust platform of antibody discovery technologies allows reaching this goal. 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. mAb humanization methods emerged as alternative for generating humanized variants of promising candidates obtained from non-human organism that could elicit an immune response. 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 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.
Part of the book: Antibody Engineering
In silico Techniques for Prospecting and Characterizing Monoclonal Antibodies
In the past few years, improvement in computational approaches provided faster and less expensive outcomes on the identification, development, and optimization of monoclonal antibodies (mAbs). In silico methods, such as homology modeling, to predict antibody structures, identification of epitope-paratope interactions, and molecular docking are useful to generate 3D structures of the antibody–antigen complexes. It helps identify the key residues involved in the antigen–antibody complex and enable modifications to enhance the antibody binding affinity. Recent advances in computational tools for redesigning antibodies are significant resources to improve antibody biophysical properties, such as binding affinity, solubility, stability, decreasing the timeframe and costs during antibody engineering. The immunobiological market grows continuously with new molecules, both natural and new molecular formats, such as bispecific antibodies, Fc-antibody fusion proteins, and mAb fragments, requiring novel methods for designing, screening, and analyzing. Algorithms and software set the in silico techniques on the innovation frontier.
Part of the book: Monoclonal Antibodies