Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells

Objectives Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Clinical & translational immunology 2020, Vol.9 (6), p.e1141-n/a, Article 1141
Hauptverfasser: Pearson, Frances E, Tullett, Kirsteen M, Leal‐Rojas, Ingrid M, Haigh, Oscar L, Masterman, Kelly‐Anne, Walpole, Carina, Bridgeman, John S, McLaren, James E, Ladell, Kristin, Miners, Kelly, Llewellyn‐Lacey, Sian, Price, David A, Tunger, Antje, Schmitz, Marc, Miles, John J, Lahoud, Mireille H, Radford, Kristen J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page n/a
container_issue 6
container_start_page e1141
container_title Clinical & translational immunology
container_volume 9
creator Pearson, Frances E
Tullett, Kirsteen M
Leal‐Rojas, Ingrid M
Haigh, Oscar L
Masterman, Kelly‐Anne
Walpole, Carina
Bridgeman, John S
McLaren, James E
Ladell, Kristin
Miners, Kelly
Llewellyn‐Lacey, Sian
Price, David A
Tunger, Antje
Schmitz, Marc
Miles, John J
Lahoud, Mireille H
Radford, Kristen J
description Objectives Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells. Methods WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming. Results The CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines. Conclusions Delivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1. This project developed a new vaccine comprising a human anti‐CLEC9A antibody fused to the immunogenic, broadly expressed tumor antigen, WT1. This vaccine specifically delivered WT1 to human CD141+ (cDC1) dendritic cells, for efficient cross‐presentation and activation of naïve and memory WT1‐specific CD8+ T cells. The anti‐CLEC9A‐WT1 antibody is a promising new vaccine candidate for malignancies that express WT1.
doi_str_mv 10.1002/cti2.1141
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_32547743</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_d7716a6649ca41f9a6290ec9da9eae79</doaj_id><sourcerecordid>2417186170</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5091-47d14817b97bc01341c616f3ffcb37d98834137041a94b013350b5b985fcaf173</originalsourceid><addsrcrecordid>eNqNksFq2zAYx83YWEvXw15gCHZYS0irz5Yt6zIobrcGArtk9ChkWc4UbKmT5Izc9gh9kz3E3mRPMjnJQjsY7GQj_b6f_hL_JHkN-AIwTi9l0OkFAIFnyXGKczzFuCifP_o_Sk69X2GMISM4h-JlcpSlOaGUZMfJw-3QC4Oq-U3FrpAwQde20cqjRnV6rRy6013v36Ew9NYhQGd3CzjfcktlULCouo5HTyJuGqeDlkiqrvPjjojJ1iIoZMTPH2sVhxrUq6jZoCj59f3B3yup2zhSXZcTtNhNvkpetKLz6nT_PUk-f7hZVLfT-aePs-pqPpU5ZjAltAFSAq0ZreV4M5AFFG3WtrLOaMPKMi5lFBMQjNQRyHJc5zUr81aKFmh2ksx23saKFb93uhduw63QfLtg3ZILF-_TKd5QCoUoCsKkINAyUaQMK8kawZRQlEXX-53rfqh71UhlghPdE-nTHaO_8KVdc5qyqIIoONsLnP06KB94r_34HMIoO3ieEiAElyTNI_r2L3RlB2fiU40UhbIAiiN1vqOks9471R7CAOZjbfhYGz7WJrJvHqc_kH9KEoFyB3xTtW291MpIdcBisXKSM5JGbaxbpYMI2prKDibE0cn_j0b6ck_rTm3-HZlXi1m6zf4bPGPqbw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417186170</pqid></control><display><type>article</type><title>Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells</title><source>DOAJ Directory of Open Access Journals</source><source>Access via Wiley Online Library</source><source>Web of Science - Science Citation Index Expanded - 2020&lt;img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /&gt;</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><creator>Pearson, Frances E ; Tullett, Kirsteen M ; Leal‐Rojas, Ingrid M ; Haigh, Oscar L ; Masterman, Kelly‐Anne ; Walpole, Carina ; Bridgeman, John S ; McLaren, James E ; Ladell, Kristin ; Miners, Kelly ; Llewellyn‐Lacey, Sian ; Price, David A ; Tunger, Antje ; Schmitz, Marc ; Miles, John J ; Lahoud, Mireille H ; Radford, Kristen J</creator><creatorcontrib>Pearson, Frances E ; Tullett, Kirsteen M ; Leal‐Rojas, Ingrid M ; Haigh, Oscar L ; Masterman, Kelly‐Anne ; Walpole, Carina ; Bridgeman, John S ; McLaren, James E ; Ladell, Kristin ; Miners, Kelly ; Llewellyn‐Lacey, Sian ; Price, David A ; Tunger, Antje ; Schmitz, Marc ; Miles, John J ; Lahoud, Mireille H ; Radford, Kristen J</creatorcontrib><description>Objectives Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells. Methods WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming. Results The CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines. Conclusions Delivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1. This project developed a new vaccine comprising a human anti‐CLEC9A antibody fused to the immunogenic, broadly expressed tumor antigen, WT1. This vaccine specifically delivered WT1 to human CD141+ (cDC1) dendritic cells, for efficient cross‐presentation and activation of naïve and memory WT1‐specific CD8+ T cells. The anti‐CLEC9A‐WT1 antibody is a promising new vaccine candidate for malignancies that express WT1.</description><identifier>ISSN: 2050-0068</identifier><identifier>EISSN: 2050-0068</identifier><identifier>DOI: 10.1002/cti2.1141</identifier><identifier>PMID: 32547743</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Antibodies ; Antigen presentation ; Antigens ; Blood &amp; organ donations ; Cancer immunotherapy ; Cancer therapies ; CD141 ; CD8 antigen ; CLEC9A ; Cytomegalovirus ; Dendritic cells ; Enzyme-linked immunosorbent assay ; Epitopes ; Hematology ; Immunogenicity ; Immunological memory ; Immunology ; Immunotherapy ; Life Sciences &amp; Biomedicine ; Lymphocytes ; Lymphocytes T ; Memory cells ; Original ; Peptides ; Science &amp; Technology ; Tumors ; Vaccines ; Wilms' tumor ; Wilms' tumor 1 ; β-Galactosidase ; γ-Interferon</subject><ispartof>Clinical &amp; translational immunology, 2020, Vol.9 (6), p.e1141-n/a, Article 1141</ispartof><rights>2020 The Authors. published by John Wiley &amp; Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.</rights><rights>2020 The Authors. Clinical &amp; Translational Immunology published by John Wiley &amp; Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>28</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000545942100006</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c5091-47d14817b97bc01341c616f3ffcb37d98834137041a94b013350b5b985fcaf173</citedby><cites>FETCH-LOGICAL-c5091-47d14817b97bc01341c616f3ffcb37d98834137041a94b013350b5b985fcaf173</cites><orcidid>0000-0002-7021-5934 ; 0000-0002-9856-2938 ; 0000-0001-9416-2737 ; 0000-0001-6512-6323 ; 0000-0001-5506-6304 ; 0000-0001-7274-9211 ; 0000-0002-9599-3396 ; 0000-0001-5022-4692 ; 0000-0002-7137-9404</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292901/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292901/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,2103,2115,4025,11567,27928,27929,27930,28253,45579,45580,46057,46481,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32547743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pearson, Frances E</creatorcontrib><creatorcontrib>Tullett, Kirsteen M</creatorcontrib><creatorcontrib>Leal‐Rojas, Ingrid M</creatorcontrib><creatorcontrib>Haigh, Oscar L</creatorcontrib><creatorcontrib>Masterman, Kelly‐Anne</creatorcontrib><creatorcontrib>Walpole, Carina</creatorcontrib><creatorcontrib>Bridgeman, John S</creatorcontrib><creatorcontrib>McLaren, James E</creatorcontrib><creatorcontrib>Ladell, Kristin</creatorcontrib><creatorcontrib>Miners, Kelly</creatorcontrib><creatorcontrib>Llewellyn‐Lacey, Sian</creatorcontrib><creatorcontrib>Price, David A</creatorcontrib><creatorcontrib>Tunger, Antje</creatorcontrib><creatorcontrib>Schmitz, Marc</creatorcontrib><creatorcontrib>Miles, John J</creatorcontrib><creatorcontrib>Lahoud, Mireille H</creatorcontrib><creatorcontrib>Radford, Kristen J</creatorcontrib><title>Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells</title><title>Clinical &amp; translational immunology</title><addtitle>CLIN TRANSL IMMUNOL</addtitle><addtitle>Clin Transl Immunology</addtitle><description>Objectives Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells. Methods WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming. Results The CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines. Conclusions Delivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1. This project developed a new vaccine comprising a human anti‐CLEC9A antibody fused to the immunogenic, broadly expressed tumor antigen, WT1. This vaccine specifically delivered WT1 to human CD141+ (cDC1) dendritic cells, for efficient cross‐presentation and activation of naïve and memory WT1‐specific CD8+ T cells. The anti‐CLEC9A‐WT1 antibody is a promising new vaccine candidate for malignancies that express WT1.</description><subject>Antibodies</subject><subject>Antigen presentation</subject><subject>Antigens</subject><subject>Blood &amp; organ donations</subject><subject>Cancer immunotherapy</subject><subject>Cancer therapies</subject><subject>CD141</subject><subject>CD8 antigen</subject><subject>CLEC9A</subject><subject>Cytomegalovirus</subject><subject>Dendritic cells</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epitopes</subject><subject>Hematology</subject><subject>Immunogenicity</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Memory cells</subject><subject>Original</subject><subject>Peptides</subject><subject>Science &amp; Technology</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>Wilms' tumor</subject><subject>Wilms' tumor 1</subject><subject>β-Galactosidase</subject><subject>γ-Interferon</subject><issn>2050-0068</issn><issn>2050-0068</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNksFq2zAYx83YWEvXw15gCHZYS0irz5Yt6zIobrcGArtk9ChkWc4UbKmT5Izc9gh9kz3E3mRPMjnJQjsY7GQj_b6f_hL_JHkN-AIwTi9l0OkFAIFnyXGKczzFuCifP_o_Sk69X2GMISM4h-JlcpSlOaGUZMfJw-3QC4Oq-U3FrpAwQde20cqjRnV6rRy6013v36Ew9NYhQGd3CzjfcktlULCouo5HTyJuGqeDlkiqrvPjjojJ1iIoZMTPH2sVhxrUq6jZoCj59f3B3yup2zhSXZcTtNhNvkpetKLz6nT_PUk-f7hZVLfT-aePs-pqPpU5ZjAltAFSAq0ZreV4M5AFFG3WtrLOaMPKMi5lFBMQjNQRyHJc5zUr81aKFmh2ksx23saKFb93uhduw63QfLtg3ZILF-_TKd5QCoUoCsKkINAyUaQMK8kawZRQlEXX-53rfqh71UhlghPdE-nTHaO_8KVdc5qyqIIoONsLnP06KB94r_34HMIoO3ieEiAElyTNI_r2L3RlB2fiU40UhbIAiiN1vqOks9471R7CAOZjbfhYGz7WJrJvHqc_kH9KEoFyB3xTtW291MpIdcBisXKSM5JGbaxbpYMI2prKDibE0cn_j0b6ck_rTm3-HZlXi1m6zf4bPGPqbw</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Pearson, Frances E</creator><creator>Tullett, Kirsteen M</creator><creator>Leal‐Rojas, Ingrid M</creator><creator>Haigh, Oscar L</creator><creator>Masterman, Kelly‐Anne</creator><creator>Walpole, Carina</creator><creator>Bridgeman, John S</creator><creator>McLaren, James E</creator><creator>Ladell, Kristin</creator><creator>Miners, Kelly</creator><creator>Llewellyn‐Lacey, Sian</creator><creator>Price, David A</creator><creator>Tunger, Antje</creator><creator>Schmitz, Marc</creator><creator>Miles, John J</creator><creator>Lahoud, Mireille H</creator><creator>Radford, Kristen J</creator><general>Wiley</general><general>John Wiley &amp; Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7021-5934</orcidid><orcidid>https://orcid.org/0000-0002-9856-2938</orcidid><orcidid>https://orcid.org/0000-0001-9416-2737</orcidid><orcidid>https://orcid.org/0000-0001-6512-6323</orcidid><orcidid>https://orcid.org/0000-0001-5506-6304</orcidid><orcidid>https://orcid.org/0000-0001-7274-9211</orcidid><orcidid>https://orcid.org/0000-0002-9599-3396</orcidid><orcidid>https://orcid.org/0000-0001-5022-4692</orcidid><orcidid>https://orcid.org/0000-0002-7137-9404</orcidid></search><sort><creationdate>2020</creationdate><title>Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells</title><author>Pearson, Frances E ; Tullett, Kirsteen M ; Leal‐Rojas, Ingrid M ; Haigh, Oscar L ; Masterman, Kelly‐Anne ; Walpole, Carina ; Bridgeman, John S ; McLaren, James E ; Ladell, Kristin ; Miners, Kelly ; Llewellyn‐Lacey, Sian ; Price, David A ; Tunger, Antje ; Schmitz, Marc ; Miles, John J ; Lahoud, Mireille H ; Radford, Kristen J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5091-47d14817b97bc01341c616f3ffcb37d98834137041a94b013350b5b985fcaf173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies</topic><topic>Antigen presentation</topic><topic>Antigens</topic><topic>Blood &amp; organ donations</topic><topic>Cancer immunotherapy</topic><topic>Cancer therapies</topic><topic>CD141</topic><topic>CD8 antigen</topic><topic>CLEC9A</topic><topic>Cytomegalovirus</topic><topic>Dendritic cells</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epitopes</topic><topic>Hematology</topic><topic>Immunogenicity</topic><topic>Immunological memory</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Life Sciences &amp; Biomedicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Memory cells</topic><topic>Original</topic><topic>Peptides</topic><topic>Science &amp; Technology</topic><topic>Tumors</topic><topic>Vaccines</topic><topic>Wilms' tumor</topic><topic>Wilms' tumor 1</topic><topic>β-Galactosidase</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pearson, Frances E</creatorcontrib><creatorcontrib>Tullett, Kirsteen M</creatorcontrib><creatorcontrib>Leal‐Rojas, Ingrid M</creatorcontrib><creatorcontrib>Haigh, Oscar L</creatorcontrib><creatorcontrib>Masterman, Kelly‐Anne</creatorcontrib><creatorcontrib>Walpole, Carina</creatorcontrib><creatorcontrib>Bridgeman, John S</creatorcontrib><creatorcontrib>McLaren, James E</creatorcontrib><creatorcontrib>Ladell, Kristin</creatorcontrib><creatorcontrib>Miners, Kelly</creatorcontrib><creatorcontrib>Llewellyn‐Lacey, Sian</creatorcontrib><creatorcontrib>Price, David A</creatorcontrib><creatorcontrib>Tunger, Antje</creatorcontrib><creatorcontrib>Schmitz, Marc</creatorcontrib><creatorcontrib>Miles, John J</creatorcontrib><creatorcontrib>Lahoud, Mireille H</creatorcontrib><creatorcontrib>Radford, Kristen J</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Clinical &amp; translational immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pearson, Frances E</au><au>Tullett, Kirsteen M</au><au>Leal‐Rojas, Ingrid M</au><au>Haigh, Oscar L</au><au>Masterman, Kelly‐Anne</au><au>Walpole, Carina</au><au>Bridgeman, John S</au><au>McLaren, James E</au><au>Ladell, Kristin</au><au>Miners, Kelly</au><au>Llewellyn‐Lacey, Sian</au><au>Price, David A</au><au>Tunger, Antje</au><au>Schmitz, Marc</au><au>Miles, John J</au><au>Lahoud, Mireille H</au><au>Radford, Kristen J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells</atitle><jtitle>Clinical &amp; translational immunology</jtitle><stitle>CLIN TRANSL IMMUNOL</stitle><addtitle>Clin Transl Immunology</addtitle><date>2020</date><risdate>2020</risdate><volume>9</volume><issue>6</issue><spage>e1141</spage><epage>n/a</epage><pages>e1141-n/a</pages><artnum>1141</artnum><issn>2050-0068</issn><eissn>2050-0068</eissn><abstract>Objectives Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells. Methods WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming. Results The CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines. Conclusions Delivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1. This project developed a new vaccine comprising a human anti‐CLEC9A antibody fused to the immunogenic, broadly expressed tumor antigen, WT1. This vaccine specifically delivered WT1 to human CD141+ (cDC1) dendritic cells, for efficient cross‐presentation and activation of naïve and memory WT1‐specific CD8+ T cells. The anti‐CLEC9A‐WT1 antibody is a promising new vaccine candidate for malignancies that express WT1.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>32547743</pmid><doi>10.1002/cti2.1141</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-7021-5934</orcidid><orcidid>https://orcid.org/0000-0002-9856-2938</orcidid><orcidid>https://orcid.org/0000-0001-9416-2737</orcidid><orcidid>https://orcid.org/0000-0001-6512-6323</orcidid><orcidid>https://orcid.org/0000-0001-5506-6304</orcidid><orcidid>https://orcid.org/0000-0001-7274-9211</orcidid><orcidid>https://orcid.org/0000-0002-9599-3396</orcidid><orcidid>https://orcid.org/0000-0001-5022-4692</orcidid><orcidid>https://orcid.org/0000-0002-7137-9404</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2050-0068
ispartof Clinical & translational immunology, 2020, Vol.9 (6), p.e1141-n/a, Article 1141
issn 2050-0068
2050-0068
language eng
recordid cdi_pubmed_primary_32547743
source DOAJ Directory of Open Access Journals; Access via Wiley Online Library; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); PubMed Central
subjects Antibodies
Antigen presentation
Antigens
Blood & organ donations
Cancer immunotherapy
Cancer therapies
CD141
CD8 antigen
CLEC9A
Cytomegalovirus
Dendritic cells
Enzyme-linked immunosorbent assay
Epitopes
Hematology
Immunogenicity
Immunological memory
Immunology
Immunotherapy
Life Sciences & Biomedicine
Lymphocytes
Lymphocytes T
Memory cells
Original
Peptides
Science & Technology
Tumors
Vaccines
Wilms' tumor
Wilms' tumor 1
β-Galactosidase
γ-Interferon
title Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T16%3A28%3A46IST&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=Human%20CLEC9A%20antibodies%20deliver%20Wilms'%20tumor%201%20(WT1)%20antigen%20to%20CD141+%20dendritic%20cells%20to%20activate%20na%C3%AFve%20and%20memory%20WT1%E2%80%90specific%20CD8+%20T%20cells&rft.jtitle=Clinical%20&%20translational%20immunology&rft.au=Pearson,%20Frances%20E&rft.date=2020&rft.volume=9&rft.issue=6&rft.spage=e1141&rft.epage=n/a&rft.pages=e1141-n/a&rft.artnum=1141&rft.issn=2050-0068&rft.eissn=2050-0068&rft_id=info:doi/10.1002/cti2.1141&rft_dat=%3Cproquest_pubme%3E2417186170%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=2417186170&rft_id=info:pmid/32547743&rft_doaj_id=oai_doaj_org_article_d7716a6649ca41f9a6290ec9da9eae79&rfr_iscdi=true