Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth
► Immunotoxins represent a promising group of targeted therapeutics for tumor patients. ► VEGFR2-specific Nanobody PE conjugated can inhibit the VEGFR2-expressing cells. ► This finding is a basis for further studies in tumor therapy in animal models. Angiogenesis targeting is an attractive approach...
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| Veröffentlicht in: | New biotechnology 2013-01, Vol.30 (2), p.205-209 |
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| creator | Behdani, Mahdi Zeinali, Sirous Karimipour, Morteza Khanahmad, Hossein Schoonooghe, Steve Aslemarz, Azam Seyed, Negar Moazami-Godarzi, Reza Baniahmad, Farzad Habibi-Anbouhi, Mahdi Hassanzadeh-Ghassabeh, Gholamreza Muyldermans, Serge |
| description | ► Immunotoxins represent a promising group of targeted therapeutics for tumor patients. ► VEGFR2-specific Nanobody PE conjugated can inhibit the VEGFR2-expressing cells. ► This finding is a basis for further studies in tumor therapy in animal models.
Angiogenesis targeting is an attractive approach for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) is such an important target that is overexpressed in tumor vasculature compared to the endothelium cells of resting blood vessels and blocking of its signaling inhibits neovascularization and tumor metastasis. Immunotoxins represent a promising group of targeted therapeutics to combat tumors. They consist of an antibody linked to a toxin and are designed to kill specifically the tumor cells. In this study, we fused a VEGFR2-specific Nanobody, the antigen-binding single-domain fragment derived from functional Heavy-chain antibody of Camelidae, to the truncated form of Pseudomonas exotoxin A and evaluated its ability to bind the VEGFR2 molecule on the cell surface. We demonstrate that this immunotoxin inhibits the proliferation of VEGFR2-expressing cells in vitro. This finding is considered to be a significant achievement in tumor therapy and it forms a basis for further studies in animal models. |
| doi_str_mv | 10.1016/j.nbt.2012.09.002 |
| format | Article |
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Angiogenesis targeting is an attractive approach for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) is such an important target that is overexpressed in tumor vasculature compared to the endothelium cells of resting blood vessels and blocking of its signaling inhibits neovascularization and tumor metastasis. Immunotoxins represent a promising group of targeted therapeutics to combat tumors. They consist of an antibody linked to a toxin and are designed to kill specifically the tumor cells. In this study, we fused a VEGFR2-specific Nanobody, the antigen-binding single-domain fragment derived from functional Heavy-chain antibody of Camelidae, to the truncated form of Pseudomonas exotoxin A and evaluated its ability to bind the VEGFR2 molecule on the cell surface. We demonstrate that this immunotoxin inhibits the proliferation of VEGFR2-expressing cells in vitro. This finding is considered to be a significant achievement in tumor therapy and it forms a basis for further studies in animal models.</description><identifier>ISSN: 1871-6784</identifier><identifier>EISSN: 1876-4347</identifier><identifier>DOI: 10.1016/j.nbt.2012.09.002</identifier><identifier>PMID: 23031816</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>ADP Ribose Transferases - pharmacology ; ADP Ribose Transferases - therapeutic use ; angiogenesis ; animal models ; antibodies ; Bacterial Toxins - pharmacology ; Bacterial Toxins - therapeutic use ; blood vessels ; Camelidae ; cell growth ; Cell Proliferation - drug effects ; Chromatography, Gel ; endothelium ; Enzyme-Linked Immunosorbent Assay ; exotoxins ; Exotoxins - pharmacology ; Exotoxins - therapeutic use ; Genetics ; HEK293 Cells ; Humans ; Immunotoxins - isolation & purification ; Immunotoxins - pharmacology ; Immunotoxins - therapeutic use ; Life Sciences ; metastasis ; neoplasm cells ; neoplasms ; Neoplasms - drug therapy ; Neoplasms - pathology ; Pseudomonas ; Pseudomonas aeruginosa Exotoxin A ; Recombinant Proteins - isolation & purification ; Single-Domain Antibodies - therapeutic use ; therapeutics ; vascular endothelial growth factor receptor-2 ; Vascular Endothelial Growth Factor Receptor-2 - immunology ; Virulence Factors - pharmacology ; Virulence Factors - therapeutic use</subject><ispartof>New biotechnology, 2013-01, Vol.30 (2), p.205-209</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-415804940026b2bbed91abf285da63c6d7b1915b76b5fb544224b76339ae95233</citedby><cites>FETCH-LOGICAL-c382t-415804940026b2bbed91abf285da63c6d7b1915b76b5fb544224b76339ae95233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.nbt.2012.09.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23031816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://riip.hal.science/pasteur-00821222$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Behdani, Mahdi</creatorcontrib><creatorcontrib>Zeinali, Sirous</creatorcontrib><creatorcontrib>Karimipour, Morteza</creatorcontrib><creatorcontrib>Khanahmad, Hossein</creatorcontrib><creatorcontrib>Schoonooghe, Steve</creatorcontrib><creatorcontrib>Aslemarz, Azam</creatorcontrib><creatorcontrib>Seyed, Negar</creatorcontrib><creatorcontrib>Moazami-Godarzi, Reza</creatorcontrib><creatorcontrib>Baniahmad, Farzad</creatorcontrib><creatorcontrib>Habibi-Anbouhi, Mahdi</creatorcontrib><creatorcontrib>Hassanzadeh-Ghassabeh, Gholamreza</creatorcontrib><creatorcontrib>Muyldermans, Serge</creatorcontrib><title>Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth</title><title>New biotechnology</title><addtitle>N Biotechnol</addtitle><description>► Immunotoxins represent a promising group of targeted therapeutics for tumor patients. ► VEGFR2-specific Nanobody PE conjugated can inhibit the VEGFR2-expressing cells. ► This finding is a basis for further studies in tumor therapy in animal models.
Angiogenesis targeting is an attractive approach for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) is such an important target that is overexpressed in tumor vasculature compared to the endothelium cells of resting blood vessels and blocking of its signaling inhibits neovascularization and tumor metastasis. Immunotoxins represent a promising group of targeted therapeutics to combat tumors. They consist of an antibody linked to a toxin and are designed to kill specifically the tumor cells. In this study, we fused a VEGFR2-specific Nanobody, the antigen-binding single-domain fragment derived from functional Heavy-chain antibody of Camelidae, to the truncated form of Pseudomonas exotoxin A and evaluated its ability to bind the VEGFR2 molecule on the cell surface. We demonstrate that this immunotoxin inhibits the proliferation of VEGFR2-expressing cells in vitro. This finding is considered to be a significant achievement in tumor therapy and it forms a basis for further studies in animal models.</description><subject>ADP Ribose Transferases - pharmacology</subject><subject>ADP Ribose Transferases - therapeutic use</subject><subject>angiogenesis</subject><subject>animal models</subject><subject>antibodies</subject><subject>Bacterial Toxins - pharmacology</subject><subject>Bacterial Toxins - therapeutic use</subject><subject>blood vessels</subject><subject>Camelidae</subject><subject>cell growth</subject><subject>Cell Proliferation - drug effects</subject><subject>Chromatography, Gel</subject><subject>endothelium</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>exotoxins</subject><subject>Exotoxins - pharmacology</subject><subject>Exotoxins - therapeutic use</subject><subject>Genetics</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunotoxins - isolation & purification</subject><subject>Immunotoxins - pharmacology</subject><subject>Immunotoxins - therapeutic use</subject><subject>Life Sciences</subject><subject>metastasis</subject><subject>neoplasm cells</subject><subject>neoplasms</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Pseudomonas</subject><subject>Pseudomonas aeruginosa Exotoxin A</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Single-Domain Antibodies - therapeutic use</subject><subject>therapeutics</subject><subject>vascular endothelial growth factor receptor-2</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - immunology</subject><subject>Virulence Factors - pharmacology</subject><subject>Virulence Factors - therapeutic use</subject><issn>1871-6784</issn><issn>1876-4347</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtu1DAUhiMEohd4ADbgF0jwLU4iVqPSC9IIqkLZWnZ8MuNREke2M7SbPjsOgS5ZHR_p_34df1n2juCCYCI-HopRx4JiQgvcFBjTF9kpqSuRc8arl3_eJBdVzU-ysxAOGAvSCPI6O6EMM1ITcZo9fYYj9G4aYIzIdejn5fXVHc3DBK3tbIu-qtFpZx7RbYDZuMGNKiB4cNE92BFtUOvGw7xTEQyKDk3eHa0BBF1i7VJpx73VNlo3Lu1xHpxHLfQ92nn3K-7fZK861Qd4-3eeZ_dXlz8ubvLtt-svF5tt3rKaxpyTssa84emLQlOtwTRE6Y7WpVGCtcJUmjSk1JXQZadLzinlaWGsUdCUlLHzLF9796qXk7eD8o_SKStvNls5qRBh9hLjmhJK6ZGkPFnzrXcheOieIYLl4l4eZHIvF_cSNwmliXm_MtOsBzDPxD_ZKfBhDXTKSbXzNsj776lBYIzLsq6XMz-tCUgujha8DIvGFoz10EZpnP3PAb8BRaGejA</recordid><startdate>20130125</startdate><enddate>20130125</enddate><creator>Behdani, Mahdi</creator><creator>Zeinali, Sirous</creator><creator>Karimipour, Morteza</creator><creator>Khanahmad, Hossein</creator><creator>Schoonooghe, Steve</creator><creator>Aslemarz, Azam</creator><creator>Seyed, Negar</creator><creator>Moazami-Godarzi, Reza</creator><creator>Baniahmad, Farzad</creator><creator>Habibi-Anbouhi, Mahdi</creator><creator>Hassanzadeh-Ghassabeh, Gholamreza</creator><creator>Muyldermans, Serge</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><scope>VOOES</scope></search><sort><creationdate>20130125</creationdate><title>Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth</title><author>Behdani, Mahdi ; Zeinali, Sirous ; Karimipour, Morteza ; Khanahmad, Hossein ; Schoonooghe, Steve ; Aslemarz, Azam ; Seyed, Negar ; Moazami-Godarzi, Reza ; Baniahmad, Farzad ; Habibi-Anbouhi, Mahdi ; Hassanzadeh-Ghassabeh, Gholamreza ; Muyldermans, Serge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-415804940026b2bbed91abf285da63c6d7b1915b76b5fb544224b76339ae95233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ADP Ribose Transferases - pharmacology</topic><topic>ADP Ribose Transferases - therapeutic use</topic><topic>angiogenesis</topic><topic>animal models</topic><topic>antibodies</topic><topic>Bacterial Toxins - pharmacology</topic><topic>Bacterial Toxins - therapeutic use</topic><topic>blood vessels</topic><topic>Camelidae</topic><topic>cell growth</topic><topic>Cell Proliferation - drug effects</topic><topic>Chromatography, Gel</topic><topic>endothelium</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>exotoxins</topic><topic>Exotoxins - pharmacology</topic><topic>Exotoxins - therapeutic use</topic><topic>Genetics</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunotoxins - isolation & purification</topic><topic>Immunotoxins - pharmacology</topic><topic>Immunotoxins - therapeutic use</topic><topic>Life Sciences</topic><topic>metastasis</topic><topic>neoplasm cells</topic><topic>neoplasms</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Pseudomonas</topic><topic>Pseudomonas aeruginosa Exotoxin A</topic><topic>Recombinant Proteins - isolation & purification</topic><topic>Single-Domain Antibodies - therapeutic use</topic><topic>therapeutics</topic><topic>vascular endothelial growth factor receptor-2</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - immunology</topic><topic>Virulence Factors - pharmacology</topic><topic>Virulence Factors - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Behdani, Mahdi</creatorcontrib><creatorcontrib>Zeinali, Sirous</creatorcontrib><creatorcontrib>Karimipour, Morteza</creatorcontrib><creatorcontrib>Khanahmad, Hossein</creatorcontrib><creatorcontrib>Schoonooghe, Steve</creatorcontrib><creatorcontrib>Aslemarz, Azam</creatorcontrib><creatorcontrib>Seyed, Negar</creatorcontrib><creatorcontrib>Moazami-Godarzi, Reza</creatorcontrib><creatorcontrib>Baniahmad, Farzad</creatorcontrib><creatorcontrib>Habibi-Anbouhi, Mahdi</creatorcontrib><creatorcontrib>Hassanzadeh-Ghassabeh, Gholamreza</creatorcontrib><creatorcontrib>Muyldermans, Serge</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>New biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Behdani, Mahdi</au><au>Zeinali, Sirous</au><au>Karimipour, Morteza</au><au>Khanahmad, Hossein</au><au>Schoonooghe, Steve</au><au>Aslemarz, Azam</au><au>Seyed, Negar</au><au>Moazami-Godarzi, Reza</au><au>Baniahmad, Farzad</au><au>Habibi-Anbouhi, Mahdi</au><au>Hassanzadeh-Ghassabeh, Gholamreza</au><au>Muyldermans, Serge</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth</atitle><jtitle>New biotechnology</jtitle><addtitle>N Biotechnol</addtitle><date>2013-01-25</date><risdate>2013</risdate><volume>30</volume><issue>2</issue><spage>205</spage><epage>209</epage><pages>205-209</pages><issn>1871-6784</issn><eissn>1876-4347</eissn><abstract>► Immunotoxins represent a promising group of targeted therapeutics for tumor patients. ► VEGFR2-specific Nanobody PE conjugated can inhibit the VEGFR2-expressing cells. ► This finding is a basis for further studies in tumor therapy in animal models.
Angiogenesis targeting is an attractive approach for cancer treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) is such an important target that is overexpressed in tumor vasculature compared to the endothelium cells of resting blood vessels and blocking of its signaling inhibits neovascularization and tumor metastasis. Immunotoxins represent a promising group of targeted therapeutics to combat tumors. They consist of an antibody linked to a toxin and are designed to kill specifically the tumor cells. In this study, we fused a VEGFR2-specific Nanobody, the antigen-binding single-domain fragment derived from functional Heavy-chain antibody of Camelidae, to the truncated form of Pseudomonas exotoxin A and evaluated its ability to bind the VEGFR2 molecule on the cell surface. We demonstrate that this immunotoxin inhibits the proliferation of VEGFR2-expressing cells in vitro. This finding is considered to be a significant achievement in tumor therapy and it forms a basis for further studies in animal models.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23031816</pmid><doi>10.1016/j.nbt.2012.09.002</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1871-6784 |
| ispartof | New biotechnology, 2013-01, Vol.30 (2), p.205-209 |
| issn | 1871-6784 1876-4347 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | ADP Ribose Transferases - pharmacology ADP Ribose Transferases - therapeutic use angiogenesis animal models antibodies Bacterial Toxins - pharmacology Bacterial Toxins - therapeutic use blood vessels Camelidae cell growth Cell Proliferation - drug effects Chromatography, Gel endothelium Enzyme-Linked Immunosorbent Assay exotoxins Exotoxins - pharmacology Exotoxins - therapeutic use Genetics HEK293 Cells Humans Immunotoxins - isolation & purification Immunotoxins - pharmacology Immunotoxins - therapeutic use Life Sciences metastasis neoplasm cells neoplasms Neoplasms - drug therapy Neoplasms - pathology Pseudomonas Pseudomonas aeruginosa Exotoxin A Recombinant Proteins - isolation & purification Single-Domain Antibodies - therapeutic use therapeutics vascular endothelial growth factor receptor-2 Vascular Endothelial Growth Factor Receptor-2 - immunology Virulence Factors - pharmacology Virulence Factors - therapeutic use |
| title | Development of VEGFR2-specific Nanobody Pseudomonas exotoxin A conjugated to provide efficient inhibition of tumor cell growth |
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