Manufacturing antibodies in the plant cell

Abstract

International audiencePlants have long been considered advantageous platforms for large-scale production of antibodies due to their low cost, scalability, and the low chances of pathogen contamination. Much effort has therefore been devoted to efficiently produce mAbs (from nanobodies to secretory antibodies) in plant cells. Several technical difficulties have been encountered and are being coped with. Improvements in production levels have been achieved by manipulation of gene expression and, more efficiently, of cell targeting and protein folding and assembly. Differences in mAb glycosylation patterns between animal and plant cells are being successfully addressed by the elimination and introduction of the appropriate enzyme activities in plant cells. Another relevant battlefield is the dichotomy between production capacity and speed. Classically, stably transformed plant lines have been proposed for large scale mAb production, whereas the use of transient expression systems has always provided production speed at the cost of scalability. However, recent advances in transient expression techniques have brought impressive yield improvements, turning speed and scalability highly compatible assets. In the era of personalized medicines, the combination of yield and speed, and the advances in glyco-engineering have made the plant cell a serious contender in the field of recombinant antibody production

Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes

“…The high accumulation of ER‐retained IgA_2A1 observed in transient fruit expression assays prompted us to use ER retention in stable versions of IgA expression. This effect has been reported repeatedly for plant‐made antibodies (Orzaez et al. , 2009) and may be indicative of a lower level of protease activity in the ER milieu.…”

Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth

“…There are two strategies of antibody engineering for plant production [32]. First, one can employ antibody in miniaturized format based on the observation that H chains retain some antigen-binding capacity even in the absence of L chains.…”

Evaluation of Unintended Effects in the Composition of Tomatoes Expressing a Human Immunoglobulin A against Rotavirus

“…43 However, to our knowledge, the metabolic signature of a therapeutic protein produced in an edible plant organ was not analyzed before. The overexpression of xenoproteins in the plant cell can induce sequence-specific responses in the host, which range from the suppression of the expression of the foreign gene via post-transcriptional gene silencing to the triggering of a general stress response or the induction of a program of cell death (see Orzaez et al 46 and references cited therein). Therefore, the accumulation of harmful compounds in response to IgA expression in fruits could not be initially dismissed.…”