Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way
The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric...
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| Veröffentlicht in: | Journal of immunotherapy 2009-09, Vol.32 (7), p.713-725 |
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| container_title | Journal of immunotherapy |
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| creator | BACHRAN, Christopher DIIRKOP, Horst SUTHERLAND, Mark BACHRAN, Diana MÜLLER, Christian WENS, Alexander MELZIG, Matthias F FUCHS, Hendrik |
| description | The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible. |
| doi_str_mv | 10.1097/cji.0b013e3181ad4052 |
| format | Article |
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Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible.</description><identifier>ISSN: 1524-9557</identifier><identifier>ISSN: 1053-8550</identifier><identifier>EISSN: 1537-4513</identifier><identifier>DOI: 10.1097/cji.0b013e3181ad4052</identifier><identifier>PMID: 19561537</identifier><identifier>CODEN: JOIMF8</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Drug Synergism ; Epidermal Growth Factor - administration & dosage ; Epidermal Growth Factor - pharmacology ; Female ; Humans ; Immunotherapy ; Immunotoxins - administration & dosage ; Immunotoxins - chemistry ; Immunotoxins - pharmacology ; Mammary Neoplasms, Experimental - drug therapy ; Mammary Neoplasms, Experimental - pathology ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Pharmacology. Drug treatments ; Receptor, Epidermal Growth Factor - genetics ; Receptor, Epidermal Growth Factor - metabolism ; Ribosome Inactivating Proteins, Type 1 - administration & dosage ; Ribosome Inactivating Proteins, Type 1 - pharmacology ; Saponins - administration & dosage ; Saponins - chemistry ; Saponins - pharmacology ; Treatment Outcome ; Triterpenes - administration & dosage ; Triterpenes - chemistry ; Triterpenes - pharmacology ; Tumor Burden - drug effects</subject><ispartof>Journal of immunotherapy, 2009-09, Vol.32 (7), p.713-725</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-766643f74a71ba8e3f2c9965718bad144cb88f1daa58d53eddfbe53ce49cde3c3</citedby><cites>FETCH-LOGICAL-c465t-766643f74a71ba8e3f2c9965718bad144cb88f1daa58d53eddfbe53ce49cde3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21793513$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19561537$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BACHRAN, Christopher</creatorcontrib><creatorcontrib>DIIRKOP, Horst</creatorcontrib><creatorcontrib>SUTHERLAND, Mark</creatorcontrib><creatorcontrib>BACHRAN, Diana</creatorcontrib><creatorcontrib>MÜLLER, Christian</creatorcontrib><creatorcontrib>WENS, Alexander</creatorcontrib><creatorcontrib>MELZIG, Matthias F</creatorcontrib><creatorcontrib>FUCHS, Hendrik</creatorcontrib><title>Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way</title><title>Journal of immunotherapy</title><addtitle>J Immunother</addtitle><description>The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Drug Synergism</subject><subject>Epidermal Growth Factor - administration & dosage</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Immunotoxins - administration & dosage</subject><subject>Immunotoxins - chemistry</subject><subject>Immunotoxins - pharmacology</subject><subject>Mammary Neoplasms, Experimental - drug therapy</subject><subject>Mammary Neoplasms, Experimental - pathology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Ribosome Inactivating Proteins, Type 1 - administration & dosage</subject><subject>Ribosome Inactivating Proteins, Type 1 - pharmacology</subject><subject>Saponins - administration & dosage</subject><subject>Saponins - chemistry</subject><subject>Saponins - pharmacology</subject><subject>Treatment Outcome</subject><subject>Triterpenes - administration & dosage</subject><subject>Triterpenes - chemistry</subject><subject>Triterpenes - pharmacology</subject><subject>Tumor Burden - drug effects</subject><issn>1524-9557</issn><issn>1053-8550</issn><issn>1537-4513</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EoqXwDxDyBXFK8cR2nByrLZRFRRy6iGM0_kjrKrEXOynk3-NVVyBx4eLx4XlmRvMS8hrYObBOvTf3_pxpBtxxaAGtYLJ-Qk5BclUJCfzp4V-LqpNSnZAXOd8zVje1qJ-TE-hkcwBPycM23HntZx8DjQPdLVNM9CrFn_Md1SvdYbp1s7N0F3_5kKkP9Is3jvpMLxNOOHuD47jS7bRP8aFwxbnBfQw-LBO9GHV5i4P0Zg0u3fpcBPod15fk2YBjdq-O9Yx8-_hht_lUXX-92m4urisjGjlXqmkawQclUIHG1vGhNl3XSAWtRgtCGN22A1hE2VrJnbWDdpIbJzpjHTf8jLx77FvW-7G4PPeTz8aNIwYXl9y3oBoAxvh_SSWkYkLxupDikTQp5pzc0O-TnzCtPbD-EE2_-bzt_42maG-OAxY9OftXOmZRgLdHAHO56pAwGJ__cDWojpdc-W9hKpk9</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>BACHRAN, Christopher</creator><creator>DIIRKOP, Horst</creator><creator>SUTHERLAND, Mark</creator><creator>BACHRAN, Diana</creator><creator>MÜLLER, Christian</creator><creator>WENS, Alexander</creator><creator>MELZIG, Matthias F</creator><creator>FUCHS, Hendrik</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</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>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20090901</creationdate><title>Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way</title><author>BACHRAN, Christopher ; DIIRKOP, Horst ; SUTHERLAND, Mark ; BACHRAN, Diana ; MÜLLER, Christian ; WENS, Alexander ; MELZIG, Matthias F ; FUCHS, Hendrik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-766643f74a71ba8e3f2c9965718bad144cb88f1daa58d53eddfbe53ce49cde3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Drug Synergism</topic><topic>Epidermal Growth Factor - administration & dosage</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Immunotoxins - administration & dosage</topic><topic>Immunotoxins - chemistry</topic><topic>Immunotoxins - pharmacology</topic><topic>Mammary Neoplasms, Experimental - drug therapy</topic><topic>Mammary Neoplasms, Experimental - pathology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptor, Epidermal Growth Factor - genetics</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Ribosome Inactivating Proteins, Type 1 - administration & dosage</topic><topic>Ribosome Inactivating Proteins, Type 1 - pharmacology</topic><topic>Saponins - administration & dosage</topic><topic>Saponins - chemistry</topic><topic>Saponins - pharmacology</topic><topic>Treatment Outcome</topic><topic>Triterpenes - administration & dosage</topic><topic>Triterpenes - chemistry</topic><topic>Triterpenes - pharmacology</topic><topic>Tumor Burden - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BACHRAN, Christopher</creatorcontrib><creatorcontrib>DIIRKOP, Horst</creatorcontrib><creatorcontrib>SUTHERLAND, Mark</creatorcontrib><creatorcontrib>BACHRAN, Diana</creatorcontrib><creatorcontrib>MÜLLER, Christian</creatorcontrib><creatorcontrib>WENS, Alexander</creatorcontrib><creatorcontrib>MELZIG, Matthias F</creatorcontrib><creatorcontrib>FUCHS, Hendrik</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BACHRAN, Christopher</au><au>DIIRKOP, Horst</au><au>SUTHERLAND, Mark</au><au>BACHRAN, Diana</au><au>MÜLLER, Christian</au><au>WENS, Alexander</au><au>MELZIG, Matthias F</au><au>FUCHS, Hendrik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way</atitle><jtitle>Journal of immunotherapy</jtitle><addtitle>J Immunother</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>32</volume><issue>7</issue><spage>713</spage><epage>725</epage><pages>713-725</pages><issn>1524-9557</issn><issn>1053-8550</issn><eissn>1537-4513</eissn><coden>JOIMF8</coden><abstract>The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. 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| identifier | ISSN: 1524-9557 |
| ispartof | Journal of immunotherapy, 2009-09, Vol.32 (7), p.713-725 |
| issn | 1524-9557 1053-8550 1537-4513 |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | Animals Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Cell Line, Tumor Cell Proliferation - drug effects Drug Synergism Epidermal Growth Factor - administration & dosage Epidermal Growth Factor - pharmacology Female Humans Immunotherapy Immunotoxins - administration & dosage Immunotoxins - chemistry Immunotoxins - pharmacology Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - pathology Medical sciences Mice Mice, Inbred BALB C Pharmacology. Drug treatments Receptor, Epidermal Growth Factor - genetics Receptor, Epidermal Growth Factor - metabolism Ribosome Inactivating Proteins, Type 1 - administration & dosage Ribosome Inactivating Proteins, Type 1 - pharmacology Saponins - administration & dosage Saponins - chemistry Saponins - pharmacology Treatment Outcome Triterpenes - administration & dosage Triterpenes - chemistry Triterpenes - pharmacology Tumor Burden - drug effects |
| title | Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way |
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