ABSTRACT
Plants are promising drug-production platforms with high economic efficiency, stability, and convenience in mass production. However, studies comparing the equivalency between the original antibodies and those produced in plants are limited. Amino acid sequences that constitute the Fab region of an antibody are diverse, and the post-transcriptional modifications that occur according to these sequences in animals and plants are also highly variable. In this study, rituximab, a blockbuster antibody drug used in the treatment of non-Hodgkin's lymphoma, was produced in Nicotiana benthamiana leaves and Arabidopsis thaliana callus, and was compared to the original rituximab produced in CHO cells. Interestingly, the epitope recognition and antigen-binding abilities of rituximab from N. benthamiana leaves were almost lost. In the case of rituximab produced in A. thaliana callus, the specific binding ability and CD20 capping activity were maintained, but the binding affinity was less than 50% of that of original rituximab from CHO cells. These results suggest that different plant species exhibit different binding affinities. Accordingly, in addition to the differences in PTMs between mammals and plants, the differences between the species must also be considered in the process of producing antibodies in plants.
Subject(s)
Antigens, CD20/metabolism , Arabidopsis/metabolism , Nicotiana/metabolism , Plant Leaves/chemistry , Rituximab/metabolism , Animals , Antibody Affinity , Antigens, CD20/chemistry , Antineoplastic Agents, Immunological/isolation & purification , Antineoplastic Agents, Immunological/metabolism , Arabidopsis/genetics , Cricetinae , Humans , Plant Leaves/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Rituximab/biosynthesis , Rituximab/genetics , Rituximab/isolation & purification , Nicotiana/geneticsABSTRACT
Thermodynamic stability of anatase nanoparticles and their transformation behaviors to rutile phase in an acidic solution was investigated in situ at two different peptization temperatures using a freeze-drying method. When peptized at 30 degrees C, the initial product was anatase with a significantly distorted atomic structure, a significant amount of hydroxyl group and Ti3+ ions, and, thus, a thermodynamically unstable state. The instability of 30 degrees C-peptized anatase was responsible for a suitable transformation to rutile later via dissolution of the anatase to form a titanium hydroxylate, followed by reprecipitation into rutile. On the other hand, 80 degrees C-peptized anatase had a relatively more ordered atomic structure, a much reduced amount of hydroxyl group, negligible Ti3+ ions, and, thus, a thermodynamically more stable state. Plausible reasons why the 80 degrees C-peptized anatase does not transform to rutile were deduced.
