CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells
We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor po...
Gespeichert in:
| Veröffentlicht in: | Integrative biology (Cambridge) 2014-08, Vol.6 (8), p.766-780 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 780 |
|---|---|
| container_issue | 8 |
| container_start_page | 766 |
| container_title | Integrative biology (Cambridge) |
| container_volume | 6 |
| creator | Myers, Dorothea E Yiv, Seang Qazi, Sanjive Ma, Hong Cely, Ingrid Shahidzadeh, Anoush Arellano, Martha Finestone, Erin Gaynon, Paul S Termuhlen, Amanda Cheng, Jianjun Uckun, Fatih M |
| description | We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells. |
| doi_str_mv | 10.1039/c4ib00095a |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4158964</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1566857666</sourcerecordid><originalsourceid>FETCH-LOGICAL-c481t-8b54be3f139e2cde19117b1fc37bcbc683d54ee5758ddda301023258c0e3b0963</originalsourceid><addsrcrecordid>eNpVUcuKFDEUDaI4D934AZKlCKVJ51GVjTDTjjo4oKAuXIUkdWs6mkrKPAT_wk-22pkedHUv3PO4h4PQE0peUMLUS8e9JYQoYe6hY9qLvlM9Ge4fdqn4ETop5RshkhPCH6KjDVeUKN4fo9_b11R1JlZ_DRGXBZyfvMPRxFScCYCDX1JJswl4SnluwVSfIk4TNvjT1_f4Y1d8BezjzltfU8bOtAIFmyUtNdVVaoRSc3MH2q7NJuLzbsngWi4rI0D7DrM32EEI5RF6MJlQ4PHtPEVf3lx83r7rrj68vdyeXXWOD7R2gxXcApsoU7BxI1BFaW_p5FhvnXVyYKPgAKIXwziOhhFKNmwjBkeAWaIkO0WvbnSXZmcYHcSaTdBL9rPJv3QyXv9_iX6nr9NPzakYlOSrwLNbgZx-tDWknn3ZRzARUiuaCikH0Uu593p-A3U5lZJhurOhRO8r1Ft-ef63wrMV_PTfx-6gh87YH66fmso</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1566857666</pqid></control><display><type>article</type><title>CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells</title><source>MEDLINE</source><source>Royal Society Of Chemistry Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Myers, Dorothea E ; Yiv, Seang ; Qazi, Sanjive ; Ma, Hong ; Cely, Ingrid ; Shahidzadeh, Anoush ; Arellano, Martha ; Finestone, Erin ; Gaynon, Paul S ; Termuhlen, Amanda ; Cheng, Jianjun ; Uckun, Fatih M</creator><creatorcontrib>Myers, Dorothea E ; Yiv, Seang ; Qazi, Sanjive ; Ma, Hong ; Cely, Ingrid ; Shahidzadeh, Anoush ; Arellano, Martha ; Finestone, Erin ; Gaynon, Paul S ; Termuhlen, Amanda ; Cheng, Jianjun ; Uckun, Fatih M</creatorcontrib><description>We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells.</description><identifier>ISSN: 1757-9694</identifier><identifier>EISSN: 1757-9708</identifier><identifier>DOI: 10.1039/c4ib00095a</identifier><identifier>PMID: 24910947</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antibodies, Monoclonal - chemistry ; Antigens, CD19 - metabolism ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Chemoradiotherapy - methods ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Liposomes - chemistry ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Electron, Transmission ; Molecular Sequence Data ; Nanoparticles - chemistry ; Neoplasm Transplantation ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Sequence Homology, Nucleic Acid ; Syk Kinase</subject><ispartof>Integrative biology (Cambridge), 2014-08, Vol.6 (8), p.766-780</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-8b54be3f139e2cde19117b1fc37bcbc683d54ee5758ddda301023258c0e3b0963</citedby><cites>FETCH-LOGICAL-c481t-8b54be3f139e2cde19117b1fc37bcbc683d54ee5758ddda301023258c0e3b0963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24910947$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Myers, Dorothea E</creatorcontrib><creatorcontrib>Yiv, Seang</creatorcontrib><creatorcontrib>Qazi, Sanjive</creatorcontrib><creatorcontrib>Ma, Hong</creatorcontrib><creatorcontrib>Cely, Ingrid</creatorcontrib><creatorcontrib>Shahidzadeh, Anoush</creatorcontrib><creatorcontrib>Arellano, Martha</creatorcontrib><creatorcontrib>Finestone, Erin</creatorcontrib><creatorcontrib>Gaynon, Paul S</creatorcontrib><creatorcontrib>Termuhlen, Amanda</creatorcontrib><creatorcontrib>Cheng, Jianjun</creatorcontrib><creatorcontrib>Uckun, Fatih M</creatorcontrib><title>CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells</title><title>Integrative biology (Cambridge)</title><addtitle>Integr Biol (Camb)</addtitle><description>We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antigens, CD19 - metabolism</subject><subject>Apoptosis</subject><subject>Base Sequence</subject><subject>Cell Line, Tumor</subject><subject>Chemoradiotherapy - methods</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</subject><subject>Liposomes - chemistry</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Microscopy, Electron, Transmission</subject><subject>Molecular Sequence Data</subject><subject>Nanoparticles - chemistry</subject><subject>Neoplasm Transplantation</subject><subject>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Syk Kinase</subject><issn>1757-9694</issn><issn>1757-9708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUcuKFDEUDaI4D934AZKlCKVJ51GVjTDTjjo4oKAuXIUkdWs6mkrKPAT_wk-22pkedHUv3PO4h4PQE0peUMLUS8e9JYQoYe6hY9qLvlM9Ge4fdqn4ETop5RshkhPCH6KjDVeUKN4fo9_b11R1JlZ_DRGXBZyfvMPRxFScCYCDX1JJswl4SnluwVSfIk4TNvjT1_f4Y1d8BezjzltfU8bOtAIFmyUtNdVVaoRSc3MH2q7NJuLzbsngWi4rI0D7DrM32EEI5RF6MJlQ4PHtPEVf3lx83r7rrj68vdyeXXWOD7R2gxXcApsoU7BxI1BFaW_p5FhvnXVyYKPgAKIXwziOhhFKNmwjBkeAWaIkO0WvbnSXZmcYHcSaTdBL9rPJv3QyXv9_iX6nr9NPzakYlOSrwLNbgZx-tDWknn3ZRzARUiuaCikH0Uu593p-A3U5lZJhurOhRO8r1Ft-ef63wrMV_PTfx-6gh87YH66fmso</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Myers, Dorothea E</creator><creator>Yiv, Seang</creator><creator>Qazi, Sanjive</creator><creator>Ma, Hong</creator><creator>Cely, Ingrid</creator><creator>Shahidzadeh, Anoush</creator><creator>Arellano, Martha</creator><creator>Finestone, Erin</creator><creator>Gaynon, Paul S</creator><creator>Termuhlen, Amanda</creator><creator>Cheng, Jianjun</creator><creator>Uckun, Fatih M</creator><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>H94</scope><scope>5PM</scope></search><sort><creationdate>20140801</creationdate><title>CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells</title><author>Myers, Dorothea E ; Yiv, Seang ; Qazi, Sanjive ; Ma, Hong ; Cely, Ingrid ; Shahidzadeh, Anoush ; Arellano, Martha ; Finestone, Erin ; Gaynon, Paul S ; Termuhlen, Amanda ; Cheng, Jianjun ; Uckun, Fatih M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-8b54be3f139e2cde19117b1fc37bcbc683d54ee5758ddda301023258c0e3b0963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Antigens, CD19 - metabolism</topic><topic>Apoptosis</topic><topic>Base Sequence</topic><topic>Cell Line, Tumor</topic><topic>Chemoradiotherapy - methods</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</topic><topic>Liposomes - chemistry</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Microscopy, Electron, Transmission</topic><topic>Molecular Sequence Data</topic><topic>Nanoparticles - chemistry</topic><topic>Neoplasm Transplantation</topic><topic>Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Syk Kinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Myers, Dorothea E</creatorcontrib><creatorcontrib>Yiv, Seang</creatorcontrib><creatorcontrib>Qazi, Sanjive</creatorcontrib><creatorcontrib>Ma, Hong</creatorcontrib><creatorcontrib>Cely, Ingrid</creatorcontrib><creatorcontrib>Shahidzadeh, Anoush</creatorcontrib><creatorcontrib>Arellano, Martha</creatorcontrib><creatorcontrib>Finestone, Erin</creatorcontrib><creatorcontrib>Gaynon, Paul S</creatorcontrib><creatorcontrib>Termuhlen, Amanda</creatorcontrib><creatorcontrib>Cheng, Jianjun</creatorcontrib><creatorcontrib>Uckun, Fatih M</creatorcontrib><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>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Integrative biology (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Myers, Dorothea E</au><au>Yiv, Seang</au><au>Qazi, Sanjive</au><au>Ma, Hong</au><au>Cely, Ingrid</au><au>Shahidzadeh, Anoush</au><au>Arellano, Martha</au><au>Finestone, Erin</au><au>Gaynon, Paul S</au><au>Termuhlen, Amanda</au><au>Cheng, Jianjun</au><au>Uckun, Fatih M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells</atitle><jtitle>Integrative biology (Cambridge)</jtitle><addtitle>Integr Biol (Camb)</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>6</volume><issue>8</issue><spage>766</spage><epage>780</epage><pages>766-780</pages><issn>1757-9694</issn><eissn>1757-9708</eissn><abstract>We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells.</abstract><cop>England</cop><pmid>24910947</pmid><doi>10.1039/c4ib00095a</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1757-9694 |
| ispartof | Integrative biology (Cambridge), 2014-08, Vol.6 (8), p.766-780 |
| issn | 1757-9694 1757-9708 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4158964 |
| source | MEDLINE; Royal Society Of Chemistry Journals; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Animals Antibodies, Monoclonal - chemistry Antigens, CD19 - metabolism Apoptosis Base Sequence Cell Line, Tumor Chemoradiotherapy - methods Drug Resistance, Neoplasm Female Gene Expression Regulation, Leukemic Humans Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Liposomes - chemistry Mice Mice, Inbred NOD Mice, SCID Microscopy, Electron, Transmission Molecular Sequence Data Nanoparticles - chemistry Neoplasm Transplantation Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism Protein-Tyrosine Kinases - antagonists & inhibitors Sequence Homology, Nucleic Acid Syk Kinase |
| title | CD19-antigen specific nanoscale liposomal formulation of a SYK P-site inhibitor causes apoptotic destruction of human B-precursor leukemia cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T22%3A20%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CD19-antigen%20specific%20nanoscale%20liposomal%20formulation%20of%20a%20SYK%20P-site%20inhibitor%20causes%20apoptotic%20destruction%20of%20human%20B-precursor%20leukemia%20cells&rft.jtitle=Integrative%20biology%20(Cambridge)&rft.au=Myers,%20Dorothea%20E&rft.date=2014-08-01&rft.volume=6&rft.issue=8&rft.spage=766&rft.epage=780&rft.pages=766-780&rft.issn=1757-9694&rft.eissn=1757-9708&rft_id=info:doi/10.1039/c4ib00095a&rft_dat=%3Cproquest_pubme%3E1566857666%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1566857666&rft_id=info:pmid/24910947&rfr_iscdi=true |