Metabolic labeling and targeted modulation of dendritic cells
Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ...
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| Veröffentlicht in: | Nature materials 2020-11, Vol.19 (11), p.1244-1252 |
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| creator | Wang, Hua Sobral, Miguel C. Zhang, David K. Y. Cartwright, Adam N. Li, Aileen Weiwei Dellacherie, Maxence O. Tringides, Christina M. Koshy, Sandeep T. Wucherpfennig, Kai W. Mooney, David J. |
| description | Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8
+
T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO–IL-15/IL-15Rα, to improve priming of antigen-specific CD8
+
T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC–T-cell interactions in vivo.
Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation. |
| doi_str_mv | 10.1038/s41563-020-0680-1 |
| format | Article |
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+
T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO–IL-15/IL-15Rα, to improve priming of antigen-specific CD8
+
T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC–T-cell interactions in vivo.
Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.</description><identifier>ISSN: 1476-1122</identifier><identifier>EISSN: 1476-4660</identifier><identifier>DOI: 10.1038/s41563-020-0680-1</identifier><identifier>PMID: 32424368</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1059/2325 ; 631/67/1059/602 ; 631/67/2321 ; 639/301/54/2295 ; Adjuvants ; Anticancer properties ; Antigens ; Azides - chemistry ; Azides - metabolism ; Biomaterials ; Biomedical materials ; Cancer Vaccines - immunology ; Cell Line, Tumor ; Chemical synthesis ; Chemistry and Materials Science ; Click Chemistry ; Condensed Matter Physics ; Conjugation ; Cytokines ; Dendritic cells ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dendritic structure ; Humans ; Hydrogels ; Immunomodulation ; Immunotherapy ; Labeling ; Lymph nodes ; Lymphocytes ; Materials Science ; Modulation ; Nanotechnology ; Optical and Electronic Materials ; Priming ; Staining and Labeling ; Tracking</subject><ispartof>Nature materials, 2020-11, Vol.19 (11), p.1244-1252</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-411a98dbc51e3174b62d019cf7f0b7fe39f494647f4b7e64ce77e9eb70b4438b3</citedby><cites>FETCH-LOGICAL-c507t-411a98dbc51e3174b62d019cf7f0b7fe39f494647f4b7e64ce77e9eb70b4438b3</cites><orcidid>0000-0002-1157-8786 ; 0000-0001-6299-1194 ; 0000-0003-2836-5813 ; 0000-0003-2747-1200 ; 0000-0002-6999-6454</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41563-020-0680-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41563-020-0680-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32424368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hua</creatorcontrib><creatorcontrib>Sobral, Miguel C.</creatorcontrib><creatorcontrib>Zhang, David K. Y.</creatorcontrib><creatorcontrib>Cartwright, Adam N.</creatorcontrib><creatorcontrib>Li, Aileen Weiwei</creatorcontrib><creatorcontrib>Dellacherie, Maxence O.</creatorcontrib><creatorcontrib>Tringides, Christina M.</creatorcontrib><creatorcontrib>Koshy, Sandeep T.</creatorcontrib><creatorcontrib>Wucherpfennig, Kai W.</creatorcontrib><creatorcontrib>Mooney, David J.</creatorcontrib><title>Metabolic labeling and targeted modulation of dendritic cells</title><title>Nature materials</title><addtitle>Nat. Mater</addtitle><addtitle>Nat Mater</addtitle><description>Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8
+
T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO–IL-15/IL-15Rα, to improve priming of antigen-specific CD8
+
T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC–T-cell interactions in vivo.
Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.</description><subject>631/67/1059/2325</subject><subject>631/67/1059/602</subject><subject>631/67/2321</subject><subject>639/301/54/2295</subject><subject>Adjuvants</subject><subject>Anticancer properties</subject><subject>Antigens</subject><subject>Azides - chemistry</subject><subject>Azides - metabolism</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Cancer Vaccines - immunology</subject><subject>Cell Line, Tumor</subject><subject>Chemical synthesis</subject><subject>Chemistry and Materials Science</subject><subject>Click Chemistry</subject><subject>Condensed Matter Physics</subject><subject>Conjugation</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic structure</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>Labeling</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Materials Science</subject><subject>Modulation</subject><subject>Nanotechnology</subject><subject>Optical and Electronic Materials</subject><subject>Priming</subject><subject>Staining and Labeling</subject><subject>Tracking</subject><issn>1476-1122</issn><issn>1476-4660</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kUFv1DAQhS0EasvSH9ALisSll8CMM7GTA0ioKm2lol7K2bKTyTZV1m7tBKn_Hq92KQWJky3NN2_mzRPiBOEjQtV8SoS1qkqQUIJqoMRX4ghJq5KUgtf7P6KUh-JtSvcAEutaHYjDSpKkSjVH4vN3nq0L09gVk3U8jX5dWN8Xs41rnrkvNqFfJjuPwRdhKHr2fRznTHc8TemdeDPYKfHx_l2JH9_Ob88uy-ubi6uzr9dlV4OeS0K0bdO7rkauUJNTsgdsu0EP4PTAVTtQS4r0QE6zoo615padBkdUNa5aiS873YfFbbjv2M_RTuYhjhsbn0ywo_m74sc7sw4_jdbUgKIscLoXiOFx4TSbzZi2FqznsCQjCfJ8aPM5V-LDP-h9WKLP9jKl80mxaXSmcEd1MaQUeXheBsFswzG7cEwOx2zDMZh73r908dzxO40MyB2QcsmvOf4Z_X_VXxCTme0</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Wang, Hua</creator><creator>Sobral, Miguel C.</creator><creator>Zhang, David K. 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Y.</au><au>Cartwright, Adam N.</au><au>Li, Aileen Weiwei</au><au>Dellacherie, Maxence O.</au><au>Tringides, Christina M.</au><au>Koshy, Sandeep T.</au><au>Wucherpfennig, Kai W.</au><au>Mooney, David J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic labeling and targeted modulation of dendritic cells</atitle><jtitle>Nature materials</jtitle><stitle>Nat. Mater</stitle><addtitle>Nat Mater</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>19</volume><issue>11</issue><spage>1244</spage><epage>1252</epage><pages>1244-1252</pages><issn>1476-1122</issn><eissn>1476-4660</eissn><abstract>Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8
+
T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO–IL-15/IL-15Rα, to improve priming of antigen-specific CD8
+
T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC–T-cell interactions in vivo.
Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32424368</pmid><doi>10.1038/s41563-020-0680-1</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1157-8786</orcidid><orcidid>https://orcid.org/0000-0001-6299-1194</orcidid><orcidid>https://orcid.org/0000-0003-2836-5813</orcidid><orcidid>https://orcid.org/0000-0003-2747-1200</orcidid><orcidid>https://orcid.org/0000-0002-6999-6454</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1059/2325 631/67/1059/602 631/67/2321 639/301/54/2295 Adjuvants Anticancer properties Antigens Azides - chemistry Azides - metabolism Biomaterials Biomedical materials Cancer Vaccines - immunology Cell Line, Tumor Chemical synthesis Chemistry and Materials Science Click Chemistry Condensed Matter Physics Conjugation Cytokines Dendritic cells Dendritic Cells - cytology Dendritic Cells - immunology Dendritic Cells - metabolism Dendritic structure Humans Hydrogels Immunomodulation Immunotherapy Labeling Lymph nodes Lymphocytes Materials Science Modulation Nanotechnology Optical and Electronic Materials Priming Staining and Labeling Tracking |
| title | Metabolic labeling and targeted modulation of dendritic cells |
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