Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library
Objective: The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatm...
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| Veröffentlicht in: | Hematology (Luxembourg) 2016-01, Vol.21 (1), p.60-67 |
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| creator | Liu, Qinghong Zhang, Chunmei Yu, Lingjia Shi, Yongyu Zhang, Liping Peng, Jun Ji, Xuebin Hou, Ming |
| description | Objective: The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatment of cardiovascular disease.
Methods: Plasma samples from patients with immune thrombocytopenia (ITP) were screened by monoclonal antibody immobilization of the platelet antigen assay and the platelet aggregation test for anti-platelet GPVI auto-antibody with an inhibitory effect. The humanized anti-platelet GPVI phage antibody was produced by phage surface display technology. The function of the phage antibody fragment against platelet aggregation was examined by the platelet aggregation test.
Results: Of 726 ITP patients, 2 (0.27%) patients' plasma significantly inhibited platelet aggregation induced by collagen-1. After five rounds of selection, enrichment, and purification, a soluble phage antibody fragment was produced, which can inhibit platelet aggregation induced by collagen-1. The results demonstrate that only a few of the screened anti-platelet GPVI auto-antibodies showed an inhibitory effect on platelet aggregation.
Discussion: A completely humanized anti-GPVI soluble phage antibody can be produced by phage surface display technology. The antibody was able to specifically block collagen-induced platelet aggregation without influencing the aggregation responses to other agonists.
Conclusions: Results of the present study suggest that very few anti-platelet GPVI auto-antibodies inhibit the aggregation function of platelet. The humanized anti-platelet GPVI produced by phage surface display technology is promising to be used to inhibit platelet aggregation in the treatment of cardiovascular disease. |
| doi_str_mv | 10.1179/1607845415Y.0000000047 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1765918803</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1765918803</sourcerecordid><originalsourceid>FETCH-LOGICAL-c347t-ad191baa562cd03555e3b579dcac674e94abdf63a5a80072f1cbc6a1532c9b903</originalsourceid><addsrcrecordid>eNqFkMlOwzAQhi0EYn-FKkcuKXYcx82xqlgqVeLAInGyxo7TGjlxsR2h8PSktCziwlxmNPPNP6MfoRHBY0J4eUkKzCc5ywl7HuNd5HwPHW8G6Way_6s-QichvGCcZZjjQ3SUFZTiDNNj9HIfu6pPXJ1AsuoaaM27rhLTrow00fk-gTaadG0haqtjsrS9cmvvojZt8jRP1itY6k9GukGm9q4ZhP50rZEefH-GDmqwQZ_v8il6vL56mN2mi7ub-Wy6SBXNeUyhIiWRAKzIVIUpY0xTyXhZKVAFz3WZg6zqggKDCcY8q4mSqgDCaKZKWWJ6ii62usOfr50OUTQmKG0ttNp1QRBesJJMJpgOaLFFlXcheF2LtTfN8KsgWGx8Fr98Fj8-D4uj3Y1ONrr6XvsydgCmW8C0tfMNvDlvKxGht87XHlplgqD_HPkAppuOPg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1765918803</pqid></control><display><type>article</type><title>Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Liu, Qinghong ; Zhang, Chunmei ; Yu, Lingjia ; Shi, Yongyu ; Zhang, Liping ; Peng, Jun ; Ji, Xuebin ; Hou, Ming</creator><creatorcontrib>Liu, Qinghong ; Zhang, Chunmei ; Yu, Lingjia ; Shi, Yongyu ; Zhang, Liping ; Peng, Jun ; Ji, Xuebin ; Hou, Ming</creatorcontrib><description>Objective: The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatment of cardiovascular disease.
Methods: Plasma samples from patients with immune thrombocytopenia (ITP) were screened by monoclonal antibody immobilization of the platelet antigen assay and the platelet aggregation test for anti-platelet GPVI auto-antibody with an inhibitory effect. The humanized anti-platelet GPVI phage antibody was produced by phage surface display technology. The function of the phage antibody fragment against platelet aggregation was examined by the platelet aggregation test.
Results: Of 726 ITP patients, 2 (0.27%) patients' plasma significantly inhibited platelet aggregation induced by collagen-1. After five rounds of selection, enrichment, and purification, a soluble phage antibody fragment was produced, which can inhibit platelet aggregation induced by collagen-1. The results demonstrate that only a few of the screened anti-platelet GPVI auto-antibodies showed an inhibitory effect on platelet aggregation.
Discussion: A completely humanized anti-GPVI soluble phage antibody can be produced by phage surface display technology. The antibody was able to specifically block collagen-induced platelet aggregation without influencing the aggregation responses to other agonists.
Conclusions: Results of the present study suggest that very few anti-platelet GPVI auto-antibodies inhibit the aggregation function of platelet. The humanized anti-platelet GPVI produced by phage surface display technology is promising to be used to inhibit platelet aggregation in the treatment of cardiovascular disease.</description><identifier>ISSN: 1607-8454</identifier><identifier>EISSN: 1607-8454</identifier><identifier>DOI: 10.1179/1607845415Y.0000000047</identifier><identifier>PMID: 26330203</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Adult ; Anti-GPVI auto-antibody ; Antibodies, Monoclonal - biosynthesis ; Antibodies, Monoclonal - pharmacology ; Blood Platelets - drug effects ; Collagen Type I - antagonists & inhibitors ; Collagen Type I - pharmacology ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression ; Humanized single chain Fv ; Humans ; Immune thrombocytopenia ; Male ; Middle Aged ; Peptide Library ; Phage surface display technology ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Membrane Glycoproteins - antagonists & inhibitors ; Platelet Membrane Glycoproteins - genetics ; Platelet Membrane Glycoproteins - immunology ; Primary Cell Culture ; Purpura, Thrombocytopenic, Idiopathic - blood ; Purpura, Thrombocytopenic, Idiopathic - immunology ; Purpura, Thrombocytopenic, Idiopathic - pathology</subject><ispartof>Hematology (Luxembourg), 2016-01, Vol.21 (1), p.60-67</ispartof><rights>W. S. Maney & Son Ltd 2015 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-ad191baa562cd03555e3b579dcac674e94abdf63a5a80072f1cbc6a1532c9b903</citedby><cites>FETCH-LOGICAL-c347t-ad191baa562cd03555e3b579dcac674e94abdf63a5a80072f1cbc6a1532c9b903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26330203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Qinghong</creatorcontrib><creatorcontrib>Zhang, Chunmei</creatorcontrib><creatorcontrib>Yu, Lingjia</creatorcontrib><creatorcontrib>Shi, Yongyu</creatorcontrib><creatorcontrib>Zhang, Liping</creatorcontrib><creatorcontrib>Peng, Jun</creatorcontrib><creatorcontrib>Ji, Xuebin</creatorcontrib><creatorcontrib>Hou, Ming</creatorcontrib><title>Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library</title><title>Hematology (Luxembourg)</title><addtitle>Hematology</addtitle><description>Objective: The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatment of cardiovascular disease.
Methods: Plasma samples from patients with immune thrombocytopenia (ITP) were screened by monoclonal antibody immobilization of the platelet antigen assay and the platelet aggregation test for anti-platelet GPVI auto-antibody with an inhibitory effect. The humanized anti-platelet GPVI phage antibody was produced by phage surface display technology. The function of the phage antibody fragment against platelet aggregation was examined by the platelet aggregation test.
Results: Of 726 ITP patients, 2 (0.27%) patients' plasma significantly inhibited platelet aggregation induced by collagen-1. After five rounds of selection, enrichment, and purification, a soluble phage antibody fragment was produced, which can inhibit platelet aggregation induced by collagen-1. The results demonstrate that only a few of the screened anti-platelet GPVI auto-antibodies showed an inhibitory effect on platelet aggregation.
Discussion: A completely humanized anti-GPVI soluble phage antibody can be produced by phage surface display technology. The antibody was able to specifically block collagen-induced platelet aggregation without influencing the aggregation responses to other agonists.
Conclusions: Results of the present study suggest that very few anti-platelet GPVI auto-antibodies inhibit the aggregation function of platelet. The humanized anti-platelet GPVI produced by phage surface display technology is promising to be used to inhibit platelet aggregation in the treatment of cardiovascular disease.</description><subject>Adult</subject><subject>Anti-GPVI auto-antibody</subject><subject>Antibodies, Monoclonal - biosynthesis</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Blood Platelets - drug effects</subject><subject>Collagen Type I - antagonists & inhibitors</subject><subject>Collagen Type I - pharmacology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humanized single chain Fv</subject><subject>Humans</subject><subject>Immune thrombocytopenia</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Peptide Library</subject><subject>Phage surface display technology</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Platelet Membrane Glycoproteins - genetics</subject><subject>Platelet Membrane Glycoproteins - immunology</subject><subject>Primary Cell Culture</subject><subject>Purpura, Thrombocytopenic, Idiopathic - blood</subject><subject>Purpura, Thrombocytopenic, Idiopathic - immunology</subject><subject>Purpura, Thrombocytopenic, Idiopathic - pathology</subject><issn>1607-8454</issn><issn>1607-8454</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMlOwzAQhi0EYn-FKkcuKXYcx82xqlgqVeLAInGyxo7TGjlxsR2h8PSktCziwlxmNPPNP6MfoRHBY0J4eUkKzCc5ywl7HuNd5HwPHW8G6Way_6s-QichvGCcZZjjQ3SUFZTiDNNj9HIfu6pPXJ1AsuoaaM27rhLTrow00fk-gTaadG0haqtjsrS9cmvvojZt8jRP1itY6k9GukGm9q4ZhP50rZEefH-GDmqwQZ_v8il6vL56mN2mi7ub-Wy6SBXNeUyhIiWRAKzIVIUpY0xTyXhZKVAFz3WZg6zqggKDCcY8q4mSqgDCaKZKWWJ6ii62usOfr50OUTQmKG0ttNp1QRBesJJMJpgOaLFFlXcheF2LtTfN8KsgWGx8Fr98Fj8-D4uj3Y1ONrr6XvsydgCmW8C0tfMNvDlvKxGht87XHlplgqD_HPkAppuOPg</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Liu, Qinghong</creator><creator>Zhang, Chunmei</creator><creator>Yu, Lingjia</creator><creator>Shi, Yongyu</creator><creator>Zhang, Liping</creator><creator>Peng, Jun</creator><creator>Ji, Xuebin</creator><creator>Hou, Ming</creator><general>Taylor & Francis</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>7X8</scope></search><sort><creationdate>20160101</creationdate><title>Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library</title><author>Liu, Qinghong ; Zhang, Chunmei ; Yu, Lingjia ; Shi, Yongyu ; Zhang, Liping ; Peng, Jun ; Ji, Xuebin ; Hou, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-ad191baa562cd03555e3b579dcac674e94abdf63a5a80072f1cbc6a1532c9b903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Anti-GPVI auto-antibody</topic><topic>Antibodies, Monoclonal - biosynthesis</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Blood Platelets - drug effects</topic><topic>Collagen Type I - antagonists & inhibitors</topic><topic>Collagen Type I - pharmacology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Humanized single chain Fv</topic><topic>Humans</topic><topic>Immune thrombocytopenia</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Peptide Library</topic><topic>Phage surface display technology</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Platelet Membrane Glycoproteins - genetics</topic><topic>Platelet Membrane Glycoproteins - immunology</topic><topic>Primary Cell Culture</topic><topic>Purpura, Thrombocytopenic, Idiopathic - blood</topic><topic>Purpura, Thrombocytopenic, Idiopathic - immunology</topic><topic>Purpura, Thrombocytopenic, Idiopathic - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Qinghong</creatorcontrib><creatorcontrib>Zhang, Chunmei</creatorcontrib><creatorcontrib>Yu, Lingjia</creatorcontrib><creatorcontrib>Shi, Yongyu</creatorcontrib><creatorcontrib>Zhang, Liping</creatorcontrib><creatorcontrib>Peng, Jun</creatorcontrib><creatorcontrib>Ji, Xuebin</creatorcontrib><creatorcontrib>Hou, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hematology (Luxembourg)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Qinghong</au><au>Zhang, Chunmei</au><au>Yu, Lingjia</au><au>Shi, Yongyu</au><au>Zhang, Liping</au><au>Peng, Jun</au><au>Ji, Xuebin</au><au>Hou, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library</atitle><jtitle>Hematology (Luxembourg)</jtitle><addtitle>Hematology</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>21</volume><issue>1</issue><spage>60</spage><epage>67</epage><pages>60-67</pages><issn>1607-8454</issn><eissn>1607-8454</eissn><abstract>Objective: The aims of the study were to study the effect of anti-platelet glycoprotein (GP) VI auto-antibodies on platelet aggregation and use phage surface display technology to produce anti-platelet GPVI phage antibody fragment, which may be developed to inhibit platelet aggregation in the treatment of cardiovascular disease.
Methods: Plasma samples from patients with immune thrombocytopenia (ITP) were screened by monoclonal antibody immobilization of the platelet antigen assay and the platelet aggregation test for anti-platelet GPVI auto-antibody with an inhibitory effect. The humanized anti-platelet GPVI phage antibody was produced by phage surface display technology. The function of the phage antibody fragment against platelet aggregation was examined by the platelet aggregation test.
Results: Of 726 ITP patients, 2 (0.27%) patients' plasma significantly inhibited platelet aggregation induced by collagen-1. After five rounds of selection, enrichment, and purification, a soluble phage antibody fragment was produced, which can inhibit platelet aggregation induced by collagen-1. The results demonstrate that only a few of the screened anti-platelet GPVI auto-antibodies showed an inhibitory effect on platelet aggregation.
Discussion: A completely humanized anti-GPVI soluble phage antibody can be produced by phage surface display technology. The antibody was able to specifically block collagen-induced platelet aggregation without influencing the aggregation responses to other agonists.
Conclusions: Results of the present study suggest that very few anti-platelet GPVI auto-antibodies inhibit the aggregation function of platelet. The humanized anti-platelet GPVI produced by phage surface display technology is promising to be used to inhibit platelet aggregation in the treatment of cardiovascular disease.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>26330203</pmid><doi>10.1179/1607845415Y.0000000047</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Anti-GPVI auto-antibody Antibodies, Monoclonal - biosynthesis Antibodies, Monoclonal - pharmacology Blood Platelets - drug effects Collagen Type I - antagonists & inhibitors Collagen Type I - pharmacology Enzyme-Linked Immunosorbent Assay Female Gene Expression Humanized single chain Fv Humans Immune thrombocytopenia Male Middle Aged Peptide Library Phage surface display technology Platelet aggregation Platelet Aggregation - drug effects Platelet Membrane Glycoproteins - antagonists & inhibitors Platelet Membrane Glycoproteins - genetics Platelet Membrane Glycoproteins - immunology Primary Cell Culture Purpura, Thrombocytopenic, Idiopathic - blood Purpura, Thrombocytopenic, Idiopathic - immunology Purpura, Thrombocytopenic, Idiopathic - pathology |
| title | Study of a humanized inhibitory anti-platelet glycoprotein VI phage antibody from a phage antibody library |
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