Development and production of protein-based biotherapeutics in mammalian cells

Abstract

Mammalian cell-derived biotherapeutics have revolutionized the treatment of various diseases, with antibodies, fusion proteins, and cytokines being their most significant successes. The so-called innovative or original products, bio-similars, and biobetters have been central pieces of this evolution, alongside the increased capacity of bioprocesses to produce them with better yields and quality. This upward trend, where Chinese hamster ovary cells represent the workhorses for large-scale production of biotherapeutics, has led to a profound and substantial generation of knowledge, methodologies, and tools applied to research, development, and innovation. Protein-biotherapeutical production is a complex bioprocess that involves a wide range of techniques, ranging from genetic engineering, followed by upstream and downstream stages up to the final product. In this chapter, we will succinctly outline the key stages to carry out successful bioprocesses with emphasis in increasing productivity and to select the appropriate methods for producing a protein for therapy. A final section, related to the modification of existing protein-biologics to improve their properties, is included aiming to generate biobet-ters or second-generation biotherapeutics. A brief description of glycoengi-neering approaches gives interesting clues to design novel long lasting bio-drugs. The main objective of the chapter is contributing to enhance the pro-duction processes of diverse biotherapeutical proteins for the economically and industrially important sector of biologics.