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Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody
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 trea...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811542/ https://www.ncbi.nlm.nih.gov/pubmed/31645587 http://dx.doi.org/10.1038/s41598-019-51656-1 |
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author | Rattanapisit, Kaewta Phakham, Tanapati Buranapraditkun, Supranee Siriwattananon, Konlavat Boonkrai, Chatikorn Pisitkun, Trairak Hirankarn, Nattiya Strasser, Richard Abe, Yoshito Phoolcharoen, Waranyoo |
author_facet | Rattanapisit, Kaewta Phakham, Tanapati Buranapraditkun, Supranee Siriwattananon, Konlavat Boonkrai, Chatikorn Pisitkun, Trairak Hirankarn, Nattiya Strasser, Richard Abe, Yoshito Phoolcharoen, Waranyoo |
author_sort | Rattanapisit, Kaewta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6811542 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68115422019-10-25 Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody Rattanapisit, Kaewta Phakham, Tanapati Buranapraditkun, Supranee Siriwattananon, Konlavat Boonkrai, Chatikorn Pisitkun, Trairak Hirankarn, Nattiya Strasser, Richard Abe, Yoshito Phoolcharoen, Waranyoo Sci Rep Article 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. Nature Publishing Group UK 2019-10-23 /pmc/articles/PMC6811542/ /pubmed/31645587 http://dx.doi.org/10.1038/s41598-019-51656-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rattanapisit, Kaewta Phakham, Tanapati Buranapraditkun, Supranee Siriwattananon, Konlavat Boonkrai, Chatikorn Pisitkun, Trairak Hirankarn, Nattiya Strasser, Richard Abe, Yoshito Phoolcharoen, Waranyoo Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title | Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title_full | Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title_fullStr | Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title_full_unstemmed | Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title_short | Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody |
title_sort | structural and in vitro functional analyses of novel plant-produced anti-human pd1 antibody |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811542/ https://www.ncbi.nlm.nih.gov/pubmed/31645587 http://dx.doi.org/10.1038/s41598-019-51656-1 |
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