Development and Production of Protein-Based Biotherapeutics in Mammalian Cells

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, biosimilars, 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 the 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, from genetic engineering, followed by upstream and downstream stages, up to the final product. In this chapter, we will succinctly outline the key stages in carrying out successful bioprocesses, with emphasis on increasing productivity, and select the appropriate methods for producing protein for therapy. The final section, related to the modification of existing protein biologics to improve their properties, is included, which aims to generate biobetters or second-generation biotherapeutics. A brief description of glycoengineering approaches gives interesting clues to the design of novel long-lasting biodrugs. The main objective of the chapter is to contribute to enhancing the production processes of diverse biotherapeutical proteins for the economically and industrially important sector of biologics.