Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies
Mesothelioma is a malignancy of the mesothelium and current treatments are generally ineffective. One promising area of anticancer drug development is to explore tumor susceptibility to targeted therapy. To achieve efficient, targeted intracellular delivery of therapeutic agents to mesothelioma cell...
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| Veröffentlicht in: | Molecular cancer therapeutics 2008-03, Vol.7 (3), p.569-578 |
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| creator | An, Feng Drummond, Daryl C Wilson, Shannon Kirpotin, Dmitri B Nishimura, Stephen L Broaddus, V Courtney Liu, Bin |
| description | Mesothelioma is a malignancy of the mesothelium and current treatments are generally ineffective. One promising area of anticancer
drug development is to explore tumor susceptibility to targeted therapy. To achieve efficient, targeted intracellular delivery
of therapeutic agents to mesothelioma cells, we selected a naive human single-chain (scFv) phage antibody display library
directly on the surface of live mesothelioma cells to identify internalizing antibodies that target mesothelioma-associated
cell surface antigens. We have identified a panel of internalizing scFvs that bind to mesothelioma cell lines derived from
both epithelioid (M28) and sarcomatous (VAMT-1) types of this disease. Most importantly, these antibodies stain mesothelioma
cells in situ and therefore define a panel of clinically represented tumor antigens. We have further exploited the internalizing function
of these scFvs to achieve targeted intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted immunoliposomes
were efficiently and specifically taken up by both epithelioid and sarcomatous mesothelioma cells, but not control cells,
and immunoliposomes encapsulating the small-molecule drug topotecan caused targeted killing of both types of mesothelioma
cells in vitro . [Mol Cancer Ther 2008;7(3):569–78] |
| doi_str_mv | 10.1158/1535-7163.MCT-07-2132 |
| format | Article |
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drug development is to explore tumor susceptibility to targeted therapy. To achieve efficient, targeted intracellular delivery
of therapeutic agents to mesothelioma cells, we selected a naive human single-chain (scFv) phage antibody display library
directly on the surface of live mesothelioma cells to identify internalizing antibodies that target mesothelioma-associated
cell surface antigens. We have identified a panel of internalizing scFvs that bind to mesothelioma cell lines derived from
both epithelioid (M28) and sarcomatous (VAMT-1) types of this disease. Most importantly, these antibodies stain mesothelioma
cells in situ and therefore define a panel of clinically represented tumor antigens. We have further exploited the internalizing function
of these scFvs to achieve targeted intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted immunoliposomes
were efficiently and specifically taken up by both epithelioid and sarcomatous mesothelioma cells, but not control cells,
and immunoliposomes encapsulating the small-molecule drug topotecan caused targeted killing of both types of mesothelioma
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drug development is to explore tumor susceptibility to targeted therapy. To achieve efficient, targeted intracellular delivery
of therapeutic agents to mesothelioma cells, we selected a naive human single-chain (scFv) phage antibody display library
directly on the surface of live mesothelioma cells to identify internalizing antibodies that target mesothelioma-associated
cell surface antigens. We have identified a panel of internalizing scFvs that bind to mesothelioma cell lines derived from
both epithelioid (M28) and sarcomatous (VAMT-1) types of this disease. Most importantly, these antibodies stain mesothelioma
cells in situ and therefore define a panel of clinically represented tumor antigens. We have further exploited the internalizing function
of these scFvs to achieve targeted intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted immunoliposomes
were efficiently and specifically taken up by both epithelioid and sarcomatous mesothelioma cells, but not control cells,
and immunoliposomes encapsulating the small-molecule drug topotecan caused targeted killing of both types of mesothelioma
cells in vitro . [Mol Cancer Ther 2008;7(3):569–78]</description><subject>Antibodies - immunology</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>Immunoglobulin Fragments - immunology</subject><subject>internalizing single-chain antibody</subject><subject>mesothelioma</subject><subject>Mesothelioma - drug therapy</subject><subject>Mesothelioma - immunology</subject><subject>phage antibody display</subject><subject>targeted therapy</subject><subject>tumor cell surface epitopes</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhSMEakvbnwDyil2Kr5_JBgmNeFQqYjN7y-PcSYwSu9hO0fTXk3RGFFasbB1_5-hen6p6A_QGQDbvQXJZa1D85ttmW1NdM-DsRXWx6E3dSBAvn-5H5rx6nfMPSqFpGZxV59BwaDlnF1XZ2tRjwY50ae5Jh6N_wHQgJZIJcyzDIsTJEofjmMmcfejJfg6u-BjsOB5IxhHd6vehYFo0_7gywzzZQFZ8xNoN1gdiQ_G72HnMV9WrvR0zXp_Oy2r7-dN287W--_7ldvPxrnaS61LrjikpwIHmXGrFAZnQTUud7JRQzlnWCKZA0RaUtELtOHPMda2iIDqk_LL6cIy9n3cTdg5DSXY098lPNh1MtN78-xL8YPr4YFgruAS2BLw7BaT4c8ZczOTz-hM2YJyz0VTQBdX_BaEVmjEpF1AeQZdizgn3f6YBatZezdqZWTszS6-GarP2uvje_r3Ks-tU5PMEg--HXz6hcTY4TAkz2uQGow03UrX8N5h1rtQ</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>An, Feng</creator><creator>Drummond, Daryl C</creator><creator>Wilson, Shannon</creator><creator>Kirpotin, Dmitri B</creator><creator>Nishimura, Stephen L</creator><creator>Broaddus, V Courtney</creator><creator>Liu, Bin</creator><general>American Association for Cancer Research</general><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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080301</creationdate><title>Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies</title><author>An, Feng ; 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One promising area of anticancer
drug development is to explore tumor susceptibility to targeted therapy. To achieve efficient, targeted intracellular delivery
of therapeutic agents to mesothelioma cells, we selected a naive human single-chain (scFv) phage antibody display library
directly on the surface of live mesothelioma cells to identify internalizing antibodies that target mesothelioma-associated
cell surface antigens. We have identified a panel of internalizing scFvs that bind to mesothelioma cell lines derived from
both epithelioid (M28) and sarcomatous (VAMT-1) types of this disease. Most importantly, these antibodies stain mesothelioma
cells in situ and therefore define a panel of clinically represented tumor antigens. We have further exploited the internalizing function
of these scFvs to achieve targeted intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted immunoliposomes
were efficiently and specifically taken up by both epithelioid and sarcomatous mesothelioma cells, but not control cells,
and immunoliposomes encapsulating the small-molecule drug topotecan caused targeted killing of both types of mesothelioma
cells in vitro . [Mol Cancer Ther 2008;7(3):569–78]</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>18319332</pmid><doi>10.1158/1535-7163.MCT-07-2132</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1535-7163 1538-8514 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antibodies - immunology Antineoplastic Agents - administration & dosage Antineoplastic Agents - therapeutic use Cell Line, Tumor Humans Immunoglobulin Fragments - immunology internalizing single-chain antibody mesothelioma Mesothelioma - drug therapy Mesothelioma - immunology phage antibody display targeted therapy tumor cell surface epitopes |
| title | Targeted drug delivery to mesothelioma cells using functionally selected internalizing human single-chain antibodies |
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