Vector-related stratagems for enhanced monoclonal antibody production in mammalian cells

Abstract

Provision of effective monoclonal antibody (mAb) based therapeutics requires careful combination of expression, selection and screening, in a suitable cell culture platform. The cell culture platform, in turn, requires high performance expression vectors for consistent and high production of mAb-based therapeutics. Further, the components of the vector need to be optimized via genetic engineering approaches, to exclude non-productive clones, reduce low secretion levels, eliminate improper functioning that affect mAb heavy chain and light chain ratio, glycosylation and aggregation, which in turn may lead to low effector functions, and to enhance productivity and post-translational processing of mAbs. This manuscript focusses on the various genetic elements that are modified and incorporated into the expression cassette, to have amplified constructs and stably expressing clones, with homogenous specificity and yield of mAbs. Production of antibodies of human origin is now possible with recombinant approaches like the gene editing tools, which enable targeted insertion of the genes coding for mAbs, using customized nucleases that enhance gene insertion. However, the ratio of light chain and heavy chain of mAb cDNA under expression, factors influencing the extent of their expression and the signal peptides for mAbs are the factors that create bottlenecks for production of mAbs, at the cellular level. This review article is focused on understanding these limitations, to overcome the challenges associated with them, and thus spur the development of mAb-based therapeutics.

Keywords: Expression vector; Gene editing; Genetic engineering; Signal peptide; Therapeutics.