Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
Identifieur interne : 000230 ( Pmc/Curation ); précédent : 000229; suivant : 000231Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
Auteurs : Raj K. Kurupati [États-Unis] ; Xiangyang Zhou [États-Unis] ; Zhiquan Xiang [États-Unis] ; Lorraine H. Keller [États-Unis] ; Hildegund C. J. Ertl [États-Unis]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2018.
Abstract
Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8+ and CD4+ T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.
The online version of this article (10.1007/s00262-018-2201-5) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1007/s00262-018-2201-5
PubMed: 30051333
PubMed Central: 7080056
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In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8<sup>+</sup> and CD4<sup>+</sup> T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8<sup>+</sup> and CD4<sup>+</sup> T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1007/s00262-018-2201-5) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Merlo, Df" uniqKey="Merlo D">DF Merlo</name></author><author><name sortKey="Rossi, L" uniqKey="Rossi L">L Rossi</name></author><author><name sortKey="Pellegrino, C" uniqKey="Pellegrino C">C Pellegrino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpson, Rm" uniqKey="Simpson R">RM Simpson</name></author><author><name sortKey="Bastian, Bc" uniqKey="Bastian B">BC Bastian</name></author><author><name sortKey="Michael, Ht" uniqKey="Michael H">HT 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancer Immunol Immunother</journal-id><journal-id journal-id-type="iso-abbrev">Cancer Immunol. Immunother</journal-id><journal-title-group><journal-title>Cancer Immunology, Immunotherapy</journal-title></journal-title-group><issn pub-type="ppub">0340-7004</issn><issn pub-type="epub">1432-0851</issn><publisher><publisher-name>Springer Berlin Heidelberg</publisher-name><publisher-loc>Berlin/Heidelberg</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30051333</article-id><article-id pub-id-type="pmc">7080056</article-id><article-id pub-id-type="publisher-id">2201</article-id><article-id pub-id-type="doi">10.1007/s00262-018-2201-5</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kurupati</surname><given-names>Raj K.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Xiangyang</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xiang</surname><given-names>Zhiquan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Keller</surname><given-names>Lorraine H.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-9795-5206</contrib-id><name><surname>Ertl</surname><given-names>Hildegund C. J.</given-names></name><address><email>ertl@wistar.org</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1956 6678</institution-id><institution-id institution-id-type="GRID">grid.251075.4</institution-id><institution>The Wistar Institute,</institution></institution-wrap>3601 Spruce Street, Philadelphia, PA 19104 USA</aff><aff id="Aff2"><label>2</label>MBF Therapeutics, Inc., 640 Woodbrook Drive, Ambler, PA 19002 USA</aff></contrib-group><pub-date pub-type="epub"><day>26</day><month>7</month><year>2018</year></pub-date><pub-date pub-type="ppub"><year>2018</year></pub-date><volume>67</volume><issue>10</issue><fpage>1533</fpage><lpage>1544</lpage><history><date date-type="received"><day>6</day><month>12</month><year>2017</year></date><date date-type="accepted"><day>6</day><month>7</month><year>2018</year></date></history><permissions><copyright-statement>© Springer-Verlag GmbH Germany, part of Springer Nature 2018</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Human immunotherapy with checkpoint blockades has achieved significant breakthroughs in recent years. In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8<sup>+</sup> and CD4<sup>+</sup> T cells secreting interferon-(IFN)-γ, tumor necrosis factor (TNF)-α, or interleukin (IL)-2 alone or in combinations in four and five out of five dogs, respectively. To avoid excessive bleeds, responses to cTrp-2 were not analyzed. All dogs responded with increased frequencies of mFAP-specific activated CD8<sup>+</sup> and CD4<sup>+</sup> T cells. The results of this safety/immunogenicity trial invite further testing of this checkpoint blockade vaccine combination in dogs with melanoma.</p><sec><title>Electronic supplementary material</title><p>The online version of this article (10.1007/s00262-018-2201-5) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Cancer</kwd><kwd>Dog</kwd><kwd>Active immunotherapy</kwd><kwd>Checkpoint blockade</kwd><kwd>Cancer-associated fibroblasts</kwd><kwd>T-cell responses</kwd></kwd-group><funding-group><award-group><funding-source><institution>MBF Therapeutics</institution></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer-Verlag GmbH Germany, part of Springer Nature 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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