Title
Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody
Author
Kaewta Rattanapisit, Tanapati Phakham, Supranee Buranapraditkun, Konlavat Siriwattananon, Chatikorn Boonkrai, Trairak Pisitkun, Nattiya Hirankarn, Richard Strasser, Yoshito Abe, Waranyoo Phoolcharoen
Year
2019
Journal
Scientific Reports
Abstract
Immunotherapy has emerged as a promising and effective treatment for cancer. The frequently used immunotherapy agents are immune checkpoint inhibitors, such as antibodies specific to PD1, PD-L1, or CTLA-4. However, these drugs are highly expensive, and most people in the world cannot access the treatment. The development of recombinant protein production platforms that are cost-effective, scalable, and safe is needed. Plant platforms are attractive because of their low production cost, speed, scalability, lack of human and animal pathogens, and post-translational modifications that enable them to produce effective monoclonal antibodies. In this study, an anti-PD1 IgG4 monoclonal antibody (mAb) was transiently produced in Nicotiana benthamiana leaves. The plant-produced anti-PD1 mAb was compared to the commercial nivolumab produced in CHO cells. Our results showed that both antibodies have similar protein structures, and the N-glycans on the plant-produced antibody lacks plant-specific structures. The PD1 binding affinity of the plant-produced and commercial nivolumab, determined by two different techniques, that is, enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR), are also comparable. Plant-produced nivolumab binds to human PD1 protein with high affinity and specificity, blocks the PD-1/PD-L1 interaction, and enhances T cell function, comparable to commercial nivolumab. These results confirmed that plant-produced anti-PD1 antibody has the potential to be effective agent for cancer immunotherapy.
Full Article
Instrument
J-720
Keywords
Circular dichroism, Secondary structure, Antibodies, Agriculture and environmental, Biochemistry