In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein
We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chai...
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| Veröffentlicht in: | The Journal of immunology (1950) 2005-04, Vol.174 (7), p.4381-4388 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 174 |
| creator | Mosquera, Luis A Card, Kimberlyn F Price-Schiavi, Shari A Belmont, Heather J Liu, Bai Builes, Janette Zhu, Xiaoyun Chavaillaz, Pierre-Andre Lee, Hyung-il Jiao, Jin-an Francis, John L Amirkhosravi, Ali Wong, Richard L Wong, Hing C |
| description | We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions. The protein is capable of forming dimers, specifically staining tumor cells and promoting target and effector cell conjugation. The protein also has potent antitumor effects in an in vivo tumor model and can mediate cell killing by Ab-dependent cellular cytotoxicity. Therefore, single-chain TCRs linked to IgG1 H chains behave like Abs but possess the ability to recognize Ags derived from intracellular targets. These fusion proteins represent a novel group of immunotherapeutics that have the potential to expand the range of tumors available for targeted therapies beyond those currently addressed by the conventional Ab-based approach. |
| doi_str_mv | 10.4049/jimmunol.174.7.4381 |
| format | Article |
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The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions. The protein is capable of forming dimers, specifically staining tumor cells and promoting target and effector cell conjugation. The protein also has potent antitumor effects in an in vivo tumor model and can mediate cell killing by Ab-dependent cellular cytotoxicity. Therefore, single-chain TCRs linked to IgG1 H chains behave like Abs but possess the ability to recognize Ags derived from intracellular targets. 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The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions. The protein is capable of forming dimers, specifically staining tumor cells and promoting target and effector cell conjugation. The protein also has potent antitumor effects in an in vivo tumor model and can mediate cell killing by Ab-dependent cellular cytotoxicity. Therefore, single-chain TCRs linked to IgG1 H chains behave like Abs but possess the ability to recognize Ags derived from intracellular targets. These fusion proteins represent a novel group of immunotherapeutics that have the potential to expand the range of tumors available for targeted therapies beyond those currently addressed by the conventional Ab-based approach.</description><subject>Antibodies, Neoplasm - chemistry</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Cell Line</subject><subject>Cytotoxicity, Immunologic</subject><subject>Dimerization</subject><subject>HLA-A2 Antigen - immunology</subject><subject>Humans</subject><subject>Immunoglobulin G - genetics</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunotherapy - methods</subject><subject>Neoplasms - therapy</subject><subject>Peptide Fragments - immunology</subject><subject>Protein Binding</subject><subject>Protein Engineering - methods</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Recombinant Fusion Proteins - therapeutic use</subject><subject>Tumor Suppressor Protein p53 - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1LwzAUhoMoOj9-gSC50qvOJE2b5FKGH4OhotPbkLbJFm0TTdoN_fV2bqJ3Xh0OPM8L57wAHGM0pIiK8xfbNJ3z9RAzOmRDmnK8BQY4y1CS5yjfBgOECEkwy9ke2I_xBSGUI0J3wR7OGOMUpQNgxw4-2zZ4qFwFv5eFh6O5CqpsdbCfqrXeQW-ggrd-oWt44Vpb-OojmdhXDR-tm9U66QXr4HT0AG-6Rjk4nl1jeNXFlXsffKutOwQ7RtVRH23mAXi6upyObpLJ3fV4dDFJSspYm9AqI4aWWOQl72_RFCtT5ZQpYYzimopCFYwXaYE4J6Z3tCJGFJiIrCoEwekBOF3nvgX_3unYysbGUte1ctp3UeYsI5xT8S-IGWOZYKgH0zVYBh9j0Ea-Bduo8CExkqsq5E8VvUMlk6sqeutkE98Vja5-nc3ve-BsDcztbL60QcvYqLrucSyXy-WfqC9jSJP0</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Mosquera, Luis A</creator><creator>Card, Kimberlyn F</creator><creator>Price-Schiavi, Shari A</creator><creator>Belmont, Heather J</creator><creator>Liu, Bai</creator><creator>Builes, Janette</creator><creator>Zhu, Xiaoyun</creator><creator>Chavaillaz, Pierre-Andre</creator><creator>Lee, Hyung-il</creator><creator>Jiao, Jin-an</creator><creator>Francis, John L</creator><creator>Amirkhosravi, Ali</creator><creator>Wong, Richard L</creator><creator>Wong, Hing C</creator><general>Am Assoc Immnol</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein</title><author>Mosquera, Luis A ; Card, Kimberlyn F ; Price-Schiavi, Shari A ; Belmont, Heather J ; Liu, Bai ; Builes, Janette ; Zhu, Xiaoyun ; Chavaillaz, Pierre-Andre ; Lee, Hyung-il ; Jiao, Jin-an ; Francis, John L ; Amirkhosravi, Ali ; Wong, Richard L ; Wong, Hing C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-4d52f4c196c8155e41afd647a9ffa8e49bab78b3b0882fc47ea2f9b1295db9213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Antibodies, Neoplasm - chemistry</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Cell Line</topic><topic>Cytotoxicity, Immunologic</topic><topic>Dimerization</topic><topic>HLA-A2 Antigen - immunology</topic><topic>Humans</topic><topic>Immunoglobulin G - genetics</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunotherapy - methods</topic><topic>Neoplasms - therapy</topic><topic>Peptide Fragments - immunology</topic><topic>Protein Binding</topic><topic>Protein Engineering - methods</topic><topic>Receptors, Antigen, T-Cell - genetics</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Recombinant Fusion Proteins - therapeutic use</topic><topic>Tumor Suppressor Protein p53 - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mosquera, Luis A</creatorcontrib><creatorcontrib>Card, Kimberlyn F</creatorcontrib><creatorcontrib>Price-Schiavi, Shari A</creatorcontrib><creatorcontrib>Belmont, Heather J</creatorcontrib><creatorcontrib>Liu, Bai</creatorcontrib><creatorcontrib>Builes, Janette</creatorcontrib><creatorcontrib>Zhu, Xiaoyun</creatorcontrib><creatorcontrib>Chavaillaz, Pierre-Andre</creatorcontrib><creatorcontrib>Lee, Hyung-il</creatorcontrib><creatorcontrib>Jiao, Jin-an</creatorcontrib><creatorcontrib>Francis, John L</creatorcontrib><creatorcontrib>Amirkhosravi, Ali</creatorcontrib><creatorcontrib>Wong, Richard L</creatorcontrib><creatorcontrib>Wong, Hing C</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>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mosquera, Luis A</au><au>Card, Kimberlyn F</au><au>Price-Schiavi, Shari A</au><au>Belmont, Heather J</au><au>Liu, Bai</au><au>Builes, Janette</au><au>Zhu, Xiaoyun</au><au>Chavaillaz, Pierre-Andre</au><au>Lee, Hyung-il</au><au>Jiao, Jin-an</au><au>Francis, John L</au><au>Amirkhosravi, Ali</au><au>Wong, Richard L</au><au>Wong, Hing C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>174</volume><issue>7</issue><spage>4381</spage><epage>4388</epage><pages>4381-4388</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. 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| subjects | Antibodies, Neoplasm - chemistry Antigens, Neoplasm - immunology Cell Line Cytotoxicity, Immunologic Dimerization HLA-A2 Antigen - immunology Humans Immunoglobulin G - genetics Immunoglobulin G - immunology Immunotherapy - methods Neoplasms - therapy Peptide Fragments - immunology Protein Binding Protein Engineering - methods Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - therapeutic use Tumor Suppressor Protein p53 - immunology |
| title | In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein |
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