Production of antibodies in plants: status after twenty years

Abstract

SummaryThanks to their potential to bind virtually all types of molecules; monoclonal antibodies are in increasing demand as therapeutics and diagnostics. To overcome the overloading of current production facilities, alternative expression systems have been developed, of which plants appear the most promising. In this review, we focus on the expression of monoclonal IgG or IgM in plant species. We analyse the data for 32 different antibodies expressed in various ways, differing in DNA construction, transformation method, signal peptide source, presence or absence of an endoplasmic reticulum retention sequence, host species and the organs tested, together resulting in 98 reported combinations. A large heterogeneity is found in the quantity and quality of the antibody produced. We discuss in more detail the strategy used to express both chains, the nature of the transcription promoters, subcellular localization and unintended proteolysis, when encountered.

Expression and glycoengineering of functionally active heteromultimeric IgM in plants

“…Although it was shown previously that plant cells are able to produce complex mammalian proteins like IgGs and IgAs (reviewed by ref. 30), the correct assembly of a human molecule that consists of 21 or 24 subunits (pentamers or hexamers) with more than 50 glycans and over 100 disulfide bonds is remarkable. In mammalian plasma cells IgMs are produced and assembled in a multistep process that stretches along the secretory pathway and requires the action of various chaperons (such as Erp44, ERGIC57) and even specialized organelles (ERGIC) (7).…”

Efficient Single Tobamoviral Vector-Based Bioproduction of Broadly Neutralizing Anti-HIV-1 Monoclonal Antibody VRC01 in Nicotiana benthamiana Plants and Utility of VRC01 in Combination Microbicides

“…Conventional IgG production in plants relies on expression of H and L chains from two independent transcription units (23,39). To develop a simple yet robust production platform, we took advantage of the subtilisin-like processing protease kex2p (40,41) and a tobamoviral replicon vector (28), whereby H and L chains are simultaneously and rapidly overexpressed from a single polypeptide transgene.…”

“…IgG molecules produced in plants, like those of human origin, are commonly glycosylated at Asn297 in the Fc region; however, the compositions of plant N-glycans slightly differ from mammalian counterparts, as represented by ␤(1,2)-linked xylose and ␣(1,3)-linked fucose (24,39,49). In fact, immunoblot analysis using plant-specific glycan-recognizing Abs (50) showed that VRC01p, but not VRC01 HEK , bear such carbohydrate structures (data not shown).…”

Production of recombinant immunotherapeutics for anticancer treatment

“…Some of these antibodies boost the immune system once in the body, but other ones do not subcellular localization, which do not allow the antibody to be correctly secreted. 37 The first mAb designed by a biomolecular engineering approach and approved by the FDA in 1997 was rituximab in the right form (correct folding and posttranslational modification) and with the desired biological function. 36 However, studies on plant-based antibodies have indicated that there are still drawbacks regarding expression, proteolytic degradation and Hodgkin lymphoma and demonstrated that 74% of the patients had an either complete or partial response, and on average, the response to the therapy persisted for six to seven months.…”