Antibody-mediated p53 protein therapy prevents liver metastasis in vivo
To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experi...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2007-02, Vol.67 (4), p.1769-1774 |
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| creator | HANSEN, James E FISCHER, Laurice K REEVES, Mark E CHAN, Grace CHANG, Sophia S BALDWIN, Scott W ARAGON, Robert J CARTER, Jacqueline J LILLY, Michael NISHIMURA, Robert N WEISBART, Richard H |
| description | To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis. |
| doi_str_mv | 10.1158/0008-5472.CAN-06-3783 |
| format | Article |
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In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-06-3783</identifier><identifier>PMID: 17308119</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antibodies, Monoclonal - genetics ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - pharmacology ; Antineoplastic agents ; Biological and medical sciences ; Cell Line, Tumor ; Colonic Neoplasms - immunology ; Colonic Neoplasms - therapy ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Immunoglobulin Fragments - genetics ; Immunoglobulin Fragments - immunology ; Immunoglobulin Fragments - pharmacology ; Liver Neoplasms, Experimental - immunology ; Liver Neoplasms, Experimental - prevention & control ; Liver Neoplasms, Experimental - secondary ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Ovarian Neoplasms - immunology ; Ovarian Neoplasms - therapy ; Pharmacology. Drug treatments ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Recombinant Fusion Proteins - pharmacology ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - immunology ; Tumor Suppressor Protein p53 - pharmacology ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2007-02, Vol.67 (4), p.1769-1774</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-4b38f4a29ffa8ca85132ca8e8aee2b5c1bffdc3ea5d3e4b7f8626b943a8e1a713</citedby><cites>FETCH-LOGICAL-c453t-4b38f4a29ffa8ca85132ca8e8aee2b5c1bffdc3ea5d3e4b7f8626b943a8e1a713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18550614$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17308119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HANSEN, James E</creatorcontrib><creatorcontrib>FISCHER, Laurice K</creatorcontrib><creatorcontrib>REEVES, Mark E</creatorcontrib><creatorcontrib>CHAN, Grace</creatorcontrib><creatorcontrib>CHANG, Sophia S</creatorcontrib><creatorcontrib>BALDWIN, Scott W</creatorcontrib><creatorcontrib>ARAGON, Robert J</creatorcontrib><creatorcontrib>CARTER, Jacqueline J</creatorcontrib><creatorcontrib>LILLY, Michael</creatorcontrib><creatorcontrib>NISHIMURA, Robert N</creatorcontrib><creatorcontrib>WEISBART, Richard H</creatorcontrib><title>Antibody-mediated p53 protein therapy prevents liver metastasis in vivo</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - genetics</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Colonic Neoplasms - immunology</subject><subject>Colonic Neoplasms - therapy</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Immunoglobulin Fragments - genetics</subject><subject>Immunoglobulin Fragments - immunology</subject><subject>Immunoglobulin Fragments - pharmacology</subject><subject>Liver Neoplasms, Experimental - immunology</subject><subject>Liver Neoplasms, Experimental - prevention & control</subject><subject>Liver Neoplasms, Experimental - secondary</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Pharmacology. Drug treatments</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Recombinant Fusion Proteins - pharmacology</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - immunology</subject><subject>Tumor Suppressor Protein p53 - pharmacology</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1LwzAUhoMobk5_gtIbvetMmo-ml2PoFIbe6HVI0xOM9GM2WWH_3pQVdykceDnwnA8ehG4JXhLC5SPGWKac5dlyvXpLsUhpLukZmhNOZZozxs_R_I-ZoSvvv2PLCeaXaEZyiiUhxRxtVm1wZVcd0gYqpwNUyY7TZNd3AVybhC_o9e4QexigDT6p3QB90kDQPpbzSYQGN3TX6MLq2sPNlAv0-fz0sX5Jt--b1_VqmxrGaUhZSaVlOius1dJoyQnNYoDUAFnJDSmtrQwFzSsKrMytFJkoC0YjQ3RO6AI9HPfGD3_24INqnDdQ17qFbu-VKHBGMyz_BUnBhWCcRZAfQdN33vdg1a53je4PimA1qlajRjVqVFG1wkKNquPc3XRgX0Z3p6nJbQTuJ0B7o2vb69Y4f-Ik51gQRn8BMQCHzQ</recordid><startdate>20070215</startdate><enddate>20070215</enddate><creator>HANSEN, James E</creator><creator>FISCHER, Laurice K</creator><creator>REEVES, Mark E</creator><creator>CHAN, Grace</creator><creator>CHANG, Sophia S</creator><creator>BALDWIN, Scott W</creator><creator>ARAGON, Robert J</creator><creator>CARTER, Jacqueline J</creator><creator>LILLY, Michael</creator><creator>NISHIMURA, Robert N</creator><creator>WEISBART, Richard H</creator><general>American Association for Cancer Research</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>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070215</creationdate><title>Antibody-mediated p53 protein therapy prevents liver metastasis in vivo</title><author>HANSEN, James E ; FISCHER, Laurice K ; REEVES, Mark E ; CHAN, Grace ; CHANG, Sophia S ; BALDWIN, Scott W ; ARAGON, Robert J ; CARTER, Jacqueline J ; LILLY, Michael ; NISHIMURA, Robert N ; WEISBART, Richard H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-4b38f4a29ffa8ca85132ca8e8aee2b5c1bffdc3ea5d3e4b7f8626b943a8e1a713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - genetics</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Colonic Neoplasms - immunology</topic><topic>Colonic Neoplasms - therapy</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Immunoglobulin Fragments - genetics</topic><topic>Immunoglobulin Fragments - immunology</topic><topic>Immunoglobulin Fragments - pharmacology</topic><topic>Liver Neoplasms, Experimental - immunology</topic><topic>Liver Neoplasms, Experimental - prevention & control</topic><topic>Liver Neoplasms, Experimental - secondary</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Pharmacology. Drug treatments</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Recombinant Fusion Proteins - pharmacology</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - immunology</topic><topic>Tumor Suppressor Protein p53 - pharmacology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HANSEN, James E</creatorcontrib><creatorcontrib>FISCHER, Laurice K</creatorcontrib><creatorcontrib>REEVES, Mark E</creatorcontrib><creatorcontrib>CHAN, Grace</creatorcontrib><creatorcontrib>CHANG, Sophia S</creatorcontrib><creatorcontrib>BALDWIN, Scott W</creatorcontrib><creatorcontrib>ARAGON, Robert J</creatorcontrib><creatorcontrib>CARTER, Jacqueline J</creatorcontrib><creatorcontrib>LILLY, Michael</creatorcontrib><creatorcontrib>NISHIMURA, Robert N</creatorcontrib><creatorcontrib>WEISBART, Richard H</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>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HANSEN, James E</au><au>FISCHER, Laurice K</au><au>REEVES, Mark E</au><au>CHAN, Grace</au><au>CHANG, Sophia S</au><au>BALDWIN, Scott W</au><au>ARAGON, Robert J</au><au>CARTER, Jacqueline J</au><au>LILLY, Michael</au><au>NISHIMURA, Robert N</au><au>WEISBART, Richard H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antibody-mediated p53 protein therapy prevents liver metastasis in vivo</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2007-02-15</date><risdate>2007</risdate><volume>67</volume><issue>4</issue><spage>1769</spage><epage>1774</epage><pages>1769-1774</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17308119</pmid><doi>10.1158/0008-5472.CAN-06-3783</doi><tpages>6</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2007-02, Vol.67 (4), p.1769-1774 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animals Antibodies, Monoclonal - genetics Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Antineoplastic agents Biological and medical sciences Cell Line, Tumor Colonic Neoplasms - immunology Colonic Neoplasms - therapy Female Gastroenterology. Liver. Pancreas. Abdomen Humans Immunoglobulin Fragments - genetics Immunoglobulin Fragments - immunology Immunoglobulin Fragments - pharmacology Liver Neoplasms, Experimental - immunology Liver Neoplasms, Experimental - prevention & control Liver Neoplasms, Experimental - secondary Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Mice Mice, Inbred BALB C Ovarian Neoplasms - immunology Ovarian Neoplasms - therapy Pharmacology. Drug treatments Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - pharmacology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - immunology Tumor Suppressor Protein p53 - pharmacology Tumors |
| title | Antibody-mediated p53 protein therapy prevents liver metastasis in vivo |
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