Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.
Identifieur interne : 000557 ( Main/Exploration ); précédent : 000556; suivant : 000558Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.
Auteurs : Tatiana V. Komarova [Russie] ; Vyacheslav S. Kosorukov ; Olga Y. Frolova ; Igor V. Petrunia ; Ksenia A. Skrypnik ; Yuri Y. Gleba ; Yuri L. DorokhovSource :
- PloS one [ 1932-6203 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Anticorps monoclonaux (isolement et purification), Anticorps monoclonaux (métabolisme), Anticorps monoclonaux (pharmacologie), Anticorps monoclonaux (usage thérapeutique), Anticorps monoclonaux humanisés (MeSH), Femelle (MeSH), Feuilles de plante (effets des médicaments et des substances chimiques), Feuilles de plante (métabolisme), Humains (MeSH), Liaison aux protéines (effets des médicaments et des substances chimiques), Lignée cellulaire tumorale (MeSH), Peptides (immunologie), Prolifération cellulaire (effets des médicaments et des substances chimiques), Récepteur ErbB-2 (métabolisme), Souris (MeSH), Tabac (métabolisme), Tests d'activité antitumorale sur modèle de xénogreffe (MeSH), Trastuzumab (MeSH), Tumeurs (anatomopathologie), Tumeurs (traitement médicamenteux), Tumeurs de l'ovaire (anatomopathologie), Épitopes (immunologie).
- MESH :
- anatomopathologie : Tumeurs, Tumeurs de l'ovaire.
- effets des médicaments et des substances chimiques : Feuilles de plante, Liaison aux protéines, Prolifération cellulaire.
- immunologie : Peptides, Épitopes.
- isolement et purification : Anticorps monoclonaux.
- métabolisme : Anticorps monoclonaux, Feuilles de plante, Récepteur ErbB-2, Tabac.
- pharmacologie : Anticorps monoclonaux.
- traitement médicamenteux : Tumeurs.
- usage thérapeutique : Anticorps monoclonaux.
- Animaux, Anticorps monoclonaux humanisés, Femelle, Humains, Lignée cellulaire tumorale, Souris, Tests d'activité antitumorale sur modèle de xénogreffe, Trastuzumab.
English descriptors
- KwdEn :
- Animals (MeSH), Antibodies, Monoclonal (isolation & purification), Antibodies, Monoclonal (metabolism), Antibodies, Monoclonal (pharmacology), Antibodies, Monoclonal (therapeutic use), Antibodies, Monoclonal, Humanized (MeSH), Cell Line, Tumor (MeSH), Cell Proliferation (drug effects), Epitopes (immunology), Female (MeSH), Humans (MeSH), Mice (MeSH), Neoplasms (drug therapy), Neoplasms (pathology), Ovarian Neoplasms (pathology), Peptides (immunology), Plant Leaves (drug effects), Plant Leaves (metabolism), Protein Binding (drug effects), Receptor, ErbB-2 (metabolism), Tobacco (metabolism), Trastuzumab (MeSH), Xenograft Model Antitumor Assays (MeSH).
- MESH :
- chemical , immunology : Epitopes, Peptides.
- chemical , isolation & purification : Antibodies, Monoclonal.
- chemical , metabolism : Antibodies, Monoclonal, Receptor, ErbB-2.
- chemical , pharmacology : Antibodies, Monoclonal.
- chemical , therapeutic use : Antibodies, Monoclonal.
- drug effects : Cell Proliferation, Plant Leaves, Protein Binding.
- drug therapy : Neoplasms.
- metabolism : Plant Leaves, Tobacco.
- pathology : Neoplasms, Ovarian Neoplasms.
- Animals, Antibodies, Monoclonal, Humanized, Cell Line, Tumor, Female, Humans, Mice, Trastuzumab, Xenograft Model Antitumor Assays.
Abstract
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.
DOI: 10.1371/journal.pone.0017541
PubMed: 21390232
PubMed Central: PMC3048398
Affiliations:
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(metabolism)</term><term>Protein Binding (drug effects)</term><term>Receptor, ErbB-2 (metabolism)</term><term>Tobacco (metabolism)</term><term>Trastuzumab (MeSH)</term><term>Xenograft Model Antitumor Assays (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Anticorps monoclonaux (isolement et purification)</term><term>Anticorps monoclonaux (métabolisme)</term><term>Anticorps monoclonaux (pharmacologie)</term><term>Anticorps monoclonaux (usage thérapeutique)</term><term>Anticorps monoclonaux humanisés (MeSH)</term><term>Femelle (MeSH)</term><term>Feuilles de plante (effets des médicaments et des substances chimiques)</term><term>Feuilles de plante (métabolisme)</term><term>Humains (MeSH)</term><term>Liaison aux protéines (effets des médicaments et des substances chimiques)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Peptides (immunologie)</term><term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term><term>Récepteur ErbB-2 (métabolisme)</term><term>Souris (MeSH)</term><term>Tabac (métabolisme)</term><term>Tests d'activité antitumorale sur modèle de xénogreffe (MeSH)</term><term>Trastuzumab (MeSH)</term><term>Tumeurs (anatomopathologie)</term><term>Tumeurs (traitement médicamenteux)</term><term>Tumeurs de l'ovaire (anatomopathologie)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Receptor, ErbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" type="chemical" 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xml:lang="fr"><term>Animaux</term><term>Anticorps monoclonaux humanisés</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Souris</term><term>Tests d'activité antitumorale sur modèle de xénogreffe</term><term>Trastuzumab</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>METHODOLOGY/PRINCIPAL FINDINGS</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS/SIGNIFICANCE</b></p><p>We conclude that PMT is active in suppression of cell proliferation and tumor growth.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21390232</PMID><DateCompleted><Year>2011</Year><Month>07</Month><Day>05</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><Issue>3</Issue><PubDate><Year>2011</Year><Month>Mar</Month><Day>03</Day></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS One</ISOAbbreviation></Journal><ArticleTitle>Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.</ArticleTitle><Pagination><MedlinePgn>e17541</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0017541</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="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.</AbstractText><AbstractText Label="METHODOLOGY/PRINCIPAL FINDINGS" NlmCategory="RESULTS">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.</AbstractText><AbstractText Label="CONCLUSIONS/SIGNIFICANCE" NlmCategory="CONCLUSIONS">We conclude that PMT is active in suppression of cell proliferation and tumor growth.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Komarova</LastName><ForeName>Tatiana V</ForeName><Initials>TV</Initials><AffiliationInfo><Affiliation>A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kosorukov</LastName><ForeName>Vyacheslav S</ForeName><Initials>VS</Initials></Author><Author ValidYN="Y"><LastName>Frolova</LastName><ForeName>Olga Y</ForeName><Initials>OY</Initials></Author><Author ValidYN="Y"><LastName>Petrunia</LastName><ForeName>Igor V</ForeName><Initials>IV</Initials></Author><Author ValidYN="Y"><LastName>Skrypnik</LastName><ForeName>Ksenia A</ForeName><Initials>KA</Initials></Author><Author ValidYN="Y"><LastName>Gleba</LastName><ForeName>Yuri Y</ForeName><Initials>YY</Initials></Author><Author ValidYN="Y"><LastName>Dorokhov</LastName><ForeName>Yuri L</ForeName><Initials>YL</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>03</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D061067">Antibodies, Monoclonal, Humanized</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000939">Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D018719">Receptor, ErbB-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>P188ANX8CK</RegistryNumber><NameOfSubstance UI="D000068878">Trastuzumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061067" MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000939" MajorTopicYN="N">Epitopes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010051" MajorTopicYN="N">Ovarian Neoplasms</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010455" MajorTopicYN="N">Peptides</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018515" MajorTopicYN="N">Plant Leaves</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018719" MajorTopicYN="N">Receptor, ErbB-2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014026" MajorTopicYN="N">Tobacco</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000068878" MajorTopicYN="N">Trastuzumab</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>09</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>02</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>3</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>3</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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