A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors
Identifieur interne : 000346 ( Ncbi/Merge ); précédent : 000345; suivant : 000347A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors
Auteurs : Catherine Gérard ; Nathalie Baudson ; Thierry Ory ; Lawrence Segal ; Jamila LouahedSource :
- Journal of Immunotherapy (Hagerstown, Md. : 1997) [ 1524-9557 ] ; 2015.
Abstract
Supplemental Digital Content is available in the text.
Url:
DOI: 10.1097/CJI.0000000000000095
PubMed: 26325375
PubMed Central: 4661047
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors</title><author><name sortKey="Gerard, Catherine" sort="Gerard, Catherine" uniqKey="Gerard C" first="Catherine" last="Gérard">Catherine Gérard</name></author><author><name sortKey="Baudson, Nathalie" sort="Baudson, Nathalie" uniqKey="Baudson N" first="Nathalie" last="Baudson">Nathalie Baudson</name></author><author><name sortKey="Ory, Thierry" sort="Ory, Thierry" uniqKey="Ory T" first="Thierry" last="Ory">Thierry Ory</name></author><author><name sortKey="Segal, Lawrence" sort="Segal, Lawrence" uniqKey="Segal L" first="Lawrence" last="Segal">Lawrence Segal</name></author><author><name sortKey="Louahed, Jamila" sort="Louahed, Jamila" uniqKey="Louahed J" first="Jamila" last="Louahed">Jamila Louahed</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26325375</idno><idno type="pmc">4661047</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661047</idno><idno type="RBID">PMC:4661047</idno><idno type="doi">10.1097/CJI.0000000000000095</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000044</idno><idno type="wicri:Area/Pmc/Curation">000044</idno><idno type="wicri:Area/Pmc/Checkpoint">000170</idno><idno type="wicri:Area/Ncbi/Merge">000346</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors</title><author><name sortKey="Gerard, Catherine" sort="Gerard, Catherine" uniqKey="Gerard C" first="Catherine" last="Gérard">Catherine Gérard</name></author><author><name sortKey="Baudson, Nathalie" sort="Baudson, Nathalie" uniqKey="Baudson N" first="Nathalie" last="Baudson">Nathalie Baudson</name></author><author><name sortKey="Ory, Thierry" sort="Ory, Thierry" uniqKey="Ory T" first="Thierry" last="Ory">Thierry Ory</name></author><author><name sortKey="Segal, Lawrence" sort="Segal, Lawrence" uniqKey="Segal L" first="Lawrence" last="Segal">Lawrence Segal</name></author><author><name sortKey="Louahed, Jamila" sort="Louahed, Jamila" uniqKey="Louahed J" first="Jamila" last="Louahed">Jamila Louahed</name></author></analytic><series><title level="j">Journal of Immunotherapy (Hagerstown, Md. : 1997)</title><idno type="ISSN">1524-9557</idno><idno type="eISSN">1537-4513</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Supplemental Digital Content is available in the text.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aldrich, Jf" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Immunother</journal-id><journal-id journal-id-type="iso-abbrev">J. Immunother</journal-id><journal-id journal-id-type="publisher-id">CJI</journal-id><journal-title-group><journal-title>Journal of Immunotherapy (Hagerstown, Md. : 1997)</journal-title></journal-title-group><issn pub-type="ppub">1524-9557</issn><issn pub-type="epub">1537-4513</issn><publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26325375</article-id><article-id pub-id-type="pmc">4661047</article-id><article-id pub-id-type="doi">10.1097/CJI.0000000000000095</article-id><article-categories><subj-group subj-group-type="heading"><subject>Basic Studies</subject></subj-group></article-categories><title-group><article-title>A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Gérard</surname><given-names>Catherine</given-names></name></contrib><contrib contrib-type="author"><name><surname>Baudson</surname><given-names>Nathalie</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ory</surname><given-names>Thierry</given-names></name></contrib><contrib contrib-type="author"><name><surname>Segal</surname><given-names>Lawrence</given-names></name></contrib><contrib contrib-type="author"><name><surname>Louahed</surname><given-names>Jamila</given-names></name></contrib></contrib-group><aff>GSK Vaccines, Rixensart, Belgium</aff><author-notes><corresp>Reprints: Catherine Gérard, GSK Vaccines, Rue de l’Institut 89, Rixensart 1330, Belgium (e-mail: <email>catherine.gerard@gsk.com</email>).</corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>18</day><month>9</month><year>2015</year></pub-date><volume>38</volume><issue>8</issue><fpage>311</fpage><lpage>320</lpage><history><date date-type="received"><day>12</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>22</day><month>7</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:type="simple" xlink:href="cji-38-311.pdf"></self-uri><abstract abstract-type="toc"><p>Supplemental Digital Content is available in the text.</p></abstract><abstract><p>The PRAME tumor antigen is a potential target for immunotherapy. We assessed the immunogenicity, the antitumor activity, and the safety and the tolerability of a recombinant PRAME protein (recPRAME) combined with the AS15 immunostimulant (recPRAME+AS15) in preclinical studies in mice and Cynomolgus monkeys. Four groups of 12 CB6F1 mice received 4 injections of phosphate-buffered saline (PBS), recPRAME, AS15, or recPRAME+AS15. Immunized mice were injected with tumor cells expressing PRAME (CT26-PRAME) 2 weeks or 2 months after the last injection. The mean tumor surface was measured twice a week. Two groups of 10 monkeys received 7 injections of saline or recPRAME+AS15. T-cell responses were measured by flow cytometry using intracellular cytokine staining (ICS). In CB6F1 mice, repeated injections of recPRAME+AS15 induced high PRAME-specific antibody titers and mostly CD4<sup>+</sup> T cells producing cytokines. This immune response was long-lasting in these animals and was associated with protection against a challenge with PRAME-expressing tumor cells (CT26-PRAME) applied either 2 weeks or 2 months after the last injection; these data indicate the induction of an immune memory. In HLA-A02.01/HLA-DR1 transgenic mice, recPRAME+AS15 induced both CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses, indicating that this antigen can be processed by the human leukocyte antigen and is potentially immunogenic in humans. In addition, a repeated-dose toxicity study in monkeys showed that 7 biweekly injections of recPRAME+AS15 were well tolerated, and induced PRAME-specific antibodies and T cells. In conclusion, these preclinical data indicate that repeated injections of the PRAME cancer immunotherapeutic are immunogenic and have an acceptable safety profile.</p></abstract><kwd-group><title>Key Words:</title><kwd>PRAME tumor antigen</kwd><kwd>AS15 immunostimulant</kwd><kwd>animal models</kwd><kwd>cancer immunotherapy</kwd><kwd>tumor protection</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>SDC</meta-name><meta-value>T</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Baudson, Nathalie" sort="Baudson, Nathalie" uniqKey="Baudson N" first="Nathalie" last="Baudson">Nathalie Baudson</name><name sortKey="Gerard, Catherine" sort="Gerard, Catherine" uniqKey="Gerard C" first="Catherine" last="Gérard">Catherine Gérard</name><name sortKey="Louahed, Jamila" sort="Louahed, Jamila" uniqKey="Louahed J" first="Jamila" last="Louahed">Jamila Louahed</name><name sortKey="Ory, Thierry" sort="Ory, Thierry" uniqKey="Ory T" first="Thierry" last="Ory">Thierry Ory</name><name sortKey="Segal, Lawrence" sort="Segal, Lawrence" uniqKey="Segal L" first="Lawrence" last="Segal">Lawrence Segal</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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