Structural and <i>In Vitro</i> Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody



Rattanapisit, Kaewta, Phakham, Tanapati, Buranapraditkun, Supranee, Siriwattananon, Konlavat, Boonkrai, Chatikorn, Pisitkun, Trairak ORCID: 0000-0001-6677-2271, Hirankarn, Nattiya, Strasser, Richard, Abe, Yoshito and Phoolcharoen, Waranyoo
(2019) Structural and <i>In Vitro</i> Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody. SCIENTIFIC REPORTS, 9 (1). 15205-.

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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.

Item Type: Article
Uncontrolled Keywords: CHO Cells, Animals, Humans, Cricetulus, Antibodies, Monoclonal, Cloning, Molecular, Biotechnology, Gene Expression, Protein Conformation, Genetic Vectors, Programmed Cell Death 1 Receptor, Nivolumab, Nicotiana
Depositing User: Symplectic Admin
Date Deposited: 21 Feb 2020 10:50
Last Modified: 02 Jan 2024 10:06
DOI: 10.1038/s41598-019-51656-1
Open Access URL: http://doi.org/10.1038/s41598-019-51656-1
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3076021