A Chemically Induced Vaccine Strategy for Prostate Cancer
Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When i...
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| Veröffentlicht in: | ACS chemical biology 2011-11, Vol.6 (11), p.1223-1231 |
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| container_title | ACS chemical biology |
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| creator | Dubrovska, Anna Kim, Chanhyuk Elliott, Jimmy Shen, Weijun Kuo, Tun-Hsun Koo, Dong-In Li, Chun Tuntland, Tove Chang, Jonathan Groessl, Todd Wu, Xu Gorney, Vanessa Ramirez-Montagut, Teresa Spiegel, David A Cho, Charles Y Schultz, Peter G |
| description | Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings. |
| doi_str_mv | 10.1021/cb200222s |
| format | Article |
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A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings.</description><identifier>ISSN: 1554-8929</identifier><identifier>EISSN: 1554-8937</identifier><identifier>DOI: 10.1021/cb200222s</identifier><identifier>PMID: 21936526</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>2,4-Dinitrophenol - chemistry ; 2,4-Dinitrophenol - immunology ; Animals ; Antibodies, Neoplasm - immunology ; Antibody-Dependent Cell Cytotoxicity - drug effects ; Antibody-Dependent Cell Cytotoxicity - immunology ; Antigens, Neoplasm - immunology ; Antigens, Surface - metabolism ; Autoantigens - immunology ; Cancer Vaccines - chemistry ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Drug Screening Assays, Antitumor ; Glutamate Carboxypeptidase II - metabolism ; Humans ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - therapy</subject><ispartof>ACS chemical biology, 2011-11, Vol.6 (11), p.1223-1231</ispartof><rights>Copyright © 2011 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a380t-63c2a94a8b4510891e8ebc16afa67230873e83d9ecfe0e053eaae9a23f1d74cf3</citedby><cites>FETCH-LOGICAL-a380t-63c2a94a8b4510891e8ebc16afa67230873e83d9ecfe0e053eaae9a23f1d74cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/cb200222s$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/cb200222s$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21936526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dubrovska, Anna</creatorcontrib><creatorcontrib>Kim, Chanhyuk</creatorcontrib><creatorcontrib>Elliott, Jimmy</creatorcontrib><creatorcontrib>Shen, Weijun</creatorcontrib><creatorcontrib>Kuo, Tun-Hsun</creatorcontrib><creatorcontrib>Koo, Dong-In</creatorcontrib><creatorcontrib>Li, Chun</creatorcontrib><creatorcontrib>Tuntland, Tove</creatorcontrib><creatorcontrib>Chang, Jonathan</creatorcontrib><creatorcontrib>Groessl, Todd</creatorcontrib><creatorcontrib>Wu, Xu</creatorcontrib><creatorcontrib>Gorney, Vanessa</creatorcontrib><creatorcontrib>Ramirez-Montagut, Teresa</creatorcontrib><creatorcontrib>Spiegel, David A</creatorcontrib><creatorcontrib>Cho, Charles Y</creatorcontrib><creatorcontrib>Schultz, Peter G</creatorcontrib><title>A Chemically Induced Vaccine Strategy for Prostate Cancer</title><title>ACS chemical biology</title><addtitle>ACS Chem. Biol</addtitle><description>Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings.</description><subject>2,4-Dinitrophenol - chemistry</subject><subject>2,4-Dinitrophenol - immunology</subject><subject>Animals</subject><subject>Antibodies, Neoplasm - immunology</subject><subject>Antibody-Dependent Cell Cytotoxicity - drug effects</subject><subject>Antibody-Dependent Cell Cytotoxicity - immunology</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antigens, Surface - metabolism</subject><subject>Autoantigens - immunology</subject><subject>Cancer Vaccines - chemistry</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Glutamate Carboxypeptidase II - metabolism</subject><subject>Humans</subject><subject>Ligands</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - therapy</subject><issn>1554-8929</issn><issn>1554-8937</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1Lw0AQhhdRbK0e_AOyFxEP0f1INrvHEqoWCgp-XMNkM6sp-ai7yaH_3khrT57mHXh4mHkJueTsjjPB720hGBNChCMy5UkSR9rI9PiQhZmQsxDWjMVSaXNKJoIbqRKhpsTMafaFTWWhrrd02ZaDxZJ-gLVVi_S199Dj55a6ztMX34V-XGkGrUV_Tk4c1AEv9nNG3h8Wb9lTtHp-XGbzVQRSsz5S0gowMegiTjjThqPGwnIFDlQqJNOpRC1Lg9YhQ5ZIBEADQjpeprF1ckZudt6N774HDH3eVMFiXUOL3RBywxI1mjQbydsdacdLg0eXb3zVgN_mnOW_ReWHokb2am8digbLA_nXzAhc7wCwIV93g2_HJ_8R_QCfNm3t</recordid><startdate>20111118</startdate><enddate>20111118</enddate><creator>Dubrovska, Anna</creator><creator>Kim, Chanhyuk</creator><creator>Elliott, Jimmy</creator><creator>Shen, Weijun</creator><creator>Kuo, Tun-Hsun</creator><creator>Koo, Dong-In</creator><creator>Li, Chun</creator><creator>Tuntland, Tove</creator><creator>Chang, Jonathan</creator><creator>Groessl, Todd</creator><creator>Wu, Xu</creator><creator>Gorney, Vanessa</creator><creator>Ramirez-Montagut, Teresa</creator><creator>Spiegel, David A</creator><creator>Cho, Charles Y</creator><creator>Schultz, Peter G</creator><general>American Chemical Society</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>20111118</creationdate><title>A Chemically Induced Vaccine Strategy for Prostate Cancer</title><author>Dubrovska, Anna ; Kim, Chanhyuk ; Elliott, Jimmy ; Shen, Weijun ; Kuo, Tun-Hsun ; Koo, Dong-In ; Li, Chun ; Tuntland, Tove ; Chang, Jonathan ; Groessl, Todd ; Wu, Xu ; Gorney, Vanessa ; Ramirez-Montagut, Teresa ; Spiegel, David A ; Cho, Charles Y ; Schultz, Peter G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a380t-63c2a94a8b4510891e8ebc16afa67230873e83d9ecfe0e053eaae9a23f1d74cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>2,4-Dinitrophenol - chemistry</topic><topic>2,4-Dinitrophenol - immunology</topic><topic>Animals</topic><topic>Antibodies, Neoplasm - immunology</topic><topic>Antibody-Dependent Cell Cytotoxicity - drug effects</topic><topic>Antibody-Dependent Cell Cytotoxicity - immunology</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antigens, Surface - metabolism</topic><topic>Autoantigens - immunology</topic><topic>Cancer Vaccines - chemistry</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Glutamate Carboxypeptidase II - metabolism</topic><topic>Humans</topic><topic>Ligands</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dubrovska, Anna</creatorcontrib><creatorcontrib>Kim, Chanhyuk</creatorcontrib><creatorcontrib>Elliott, Jimmy</creatorcontrib><creatorcontrib>Shen, Weijun</creatorcontrib><creatorcontrib>Kuo, Tun-Hsun</creatorcontrib><creatorcontrib>Koo, Dong-In</creatorcontrib><creatorcontrib>Li, Chun</creatorcontrib><creatorcontrib>Tuntland, Tove</creatorcontrib><creatorcontrib>Chang, Jonathan</creatorcontrib><creatorcontrib>Groessl, Todd</creatorcontrib><creatorcontrib>Wu, Xu</creatorcontrib><creatorcontrib>Gorney, Vanessa</creatorcontrib><creatorcontrib>Ramirez-Montagut, Teresa</creatorcontrib><creatorcontrib>Spiegel, David A</creatorcontrib><creatorcontrib>Cho, Charles Y</creatorcontrib><creatorcontrib>Schultz, Peter G</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>ACS chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dubrovska, Anna</au><au>Kim, Chanhyuk</au><au>Elliott, Jimmy</au><au>Shen, Weijun</au><au>Kuo, Tun-Hsun</au><au>Koo, Dong-In</au><au>Li, Chun</au><au>Tuntland, Tove</au><au>Chang, Jonathan</au><au>Groessl, Todd</au><au>Wu, Xu</au><au>Gorney, Vanessa</au><au>Ramirez-Montagut, Teresa</au><au>Spiegel, David A</au><au>Cho, Charles Y</au><au>Schultz, Peter G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Chemically Induced Vaccine Strategy for Prostate Cancer</atitle><jtitle>ACS chemical biology</jtitle><addtitle>ACS Chem. Biol</addtitle><date>2011-11-18</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>1223</spage><epage>1231</epage><pages>1223-1231</pages><issn>1554-8929</issn><eissn>1554-8937</eissn><abstract>Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. 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| ispartof | ACS chemical biology, 2011-11, Vol.6 (11), p.1223-1231 |
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| subjects | 2,4-Dinitrophenol - chemistry 2,4-Dinitrophenol - immunology Animals Antibodies, Neoplasm - immunology Antibody-Dependent Cell Cytotoxicity - drug effects Antibody-Dependent Cell Cytotoxicity - immunology Antigens, Neoplasm - immunology Antigens, Surface - metabolism Autoantigens - immunology Cancer Vaccines - chemistry Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cell Proliferation - drug effects Cell Survival - drug effects Drug Screening Assays, Antitumor Glutamate Carboxypeptidase II - metabolism Humans Ligands Male Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Prostatic Neoplasms - immunology Prostatic Neoplasms - pathology Prostatic Neoplasms - therapy |
| title | A Chemically Induced Vaccine Strategy for Prostate Cancer |
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