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Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth
BACKGROUND: Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048398/ https://www.ncbi.nlm.nih.gov/pubmed/21390232 http://dx.doi.org/10.1371/journal.pone.0017541 |
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author | Komarova, Tatiana V. Kosorukov, Vyacheslav S. Frolova, Olga Y. Petrunia, Igor V. Skrypnik, Ksenia A. Gleba, Yuri Y. Dorokhov, Yuri L. |
author_facet | Komarova, Tatiana V. Kosorukov, Vyacheslav S. Frolova, Olga Y. Petrunia, Igor V. Skrypnik, Ksenia A. Gleba, Yuri Y. Dorokhov, Yuri L. |
author_sort | Komarova, Tatiana V. |
collection | PubMed |
description | BACKGROUND: Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells. METHODOLOGY/PRINCIPAL FINDINGS: We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells. CONCLUSIONS/SIGNIFICANCE: We conclude that PMT is active in suppression of cell proliferation and tumor growth. |
format | Text |
id | pubmed-3048398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30483982011-03-09 Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth Komarova, Tatiana V. Kosorukov, Vyacheslav S. Frolova, Olga Y. Petrunia, Igor V. Skrypnik, Ksenia A. Gleba, Yuri Y. Dorokhov, Yuri L. PLoS One Research Article BACKGROUND: Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells. METHODOLOGY/PRINCIPAL FINDINGS: We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells. CONCLUSIONS/SIGNIFICANCE: We conclude that PMT is active in suppression of cell proliferation and tumor growth. Public Library of Science 2011-03-03 /pmc/articles/PMC3048398/ /pubmed/21390232 http://dx.doi.org/10.1371/journal.pone.0017541 Text en Komarova et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Komarova, Tatiana V. Kosorukov, Vyacheslav S. Frolova, Olga Y. Petrunia, Igor V. Skrypnik, Ksenia A. Gleba, Yuri Y. Dorokhov, Yuri L. Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title | Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title_full | Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title_fullStr | Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title_full_unstemmed | Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title_short | Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth |
title_sort | plant-made trastuzumab (herceptin) inhibits her2/neu+ cell proliferation and retards tumor growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048398/ https://www.ncbi.nlm.nih.gov/pubmed/21390232 http://dx.doi.org/10.1371/journal.pone.0017541 |
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