Recombinant antibody production evolves into multiple options aimed at yielding reagents suitable for application-specific needs

Abstract

BackgroundAntibodies have been a pillar of basic research, while their relevance in clinical diagnostics and therapy is constantly growing. Consequently, the production of both conventional and fragment antibodies constantly faces more demanding challenges for the improvement of their quantity and quality. The answer to such an increasing need has been the development of a wide array of formats and alternative production platforms. This review offers a critical comparison and evaluation of the different options to help the researchers interested in expressing recombinant antibodies in their choice.ResultsRather than the compilation of an exhaustive list of the recent publications in the field, this review intendeds to analyze the development of the most innovative or fast-growing strategies. These have been illustrated with some significant examples and, when possible, compared with the existing alternatives. Space has also been given to those solutions that might represent interesting opportunities or that investigate critical aspects of the production optimization but for which the available data as yet do not allow for a definitive judgment.ConclusionsThe take-home message is that there is a clear process of progressive diversification concerning the antibody expression platforms and an effort to yield directly application-adapted immune-reagents rather than generic naked antibodies that need further in vitro modification steps before becoming usable.

Considerations for the Design of Antibody-Based Therapeutics

“…Antibody genes can be transformed into plants via the transfer DNA of Agrobacterium tumefaciens, which allows for purification of protein from tobacco leaves or rice seeds. 137,148 Alternatively, antibodies can be harvested from mouse or goat milk or chicken eggs using transgenic animals that have human Ig genes in place of the native Ig loci. 137 While these latter systems are expected to produce proteins with human-like glycosylation, plant systems have been engineered to prevent the attachment of potentially immunogenic sugars such as xylose.…”

A long non-coding SINEUP RNA boosts semi-stable production of fully human monoclonal antibodies in HEK293E cells

“…The first class comprises simple organisms as prokaryotic, yeast, fungi or insect cells whose advantages are low costs and good productivity (in the high mg/L range) 5 . Sub-optimal folding and a very different pattern of glycosylation make these systems useful for production of simple non-glycosylated proteins, or for generation of preliminary binding data.…”

Engineered cross‐reacting nanobodies simplify comparative oncology between humans and dogs

“…Nanobodies are antibody fragments which correspond to the variable region of the heavy‐chain‐only antibodies (VHH) of Camelidae origin. They know a constantly growing interest because of their small mass (14 kDa), high stability and simplicity in being mutated and functionalized . In this study, we show that an anti‐human epidermal growth factor receptor 2 (HER2) nanobody isolated from a pre‐immune library recognized also the canine protein homologue DER2.…”