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...
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Veröffentlicht in: | Clinical & translational immunology 2020, Vol.9 (6), p.e1141-n/a, Article 1141 |
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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 |
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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 & 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</subject><ispartof>Clinical & translational immunology, 2020, Vol.9 (6), p.e1141-n/a, Article 1141</ispartof><rights>2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.</rights><rights>2020 The Authors. Clinical & Translational Immunology published by John Wiley & 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 & 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 & 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 & Biomedicine</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Memory cells</subject><subject>Original</subject><subject>Peptides</subject><subject>Science & 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 & 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 & 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 & Biomedicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Memory cells</topic><topic>Original</topic><topic>Peptides</topic><topic>Science & 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 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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 & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & 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 & 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 & 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 |
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