Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
Identifieur interne : 000D95 ( Main/Exploration ); précédent : 000D94; suivant : 000D96Safety 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
Affiliations:
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Kurupati</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>3601 Spruce Street, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Zhou, Xiangyang" sort="Zhou, Xiangyang" uniqKey="Zhou X" first="Xiangyang" last="Zhou">Xiangyang Zhou</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>3601 Spruce Street, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Xiang, Zhiquan" sort="Xiang, Zhiquan" uniqKey="Xiang Z" first="Zhiquan" last="Xiang">Zhiquan Xiang</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>3601 Spruce Street, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Keller, Lorraine H" sort="Keller, Lorraine H" uniqKey="Keller L" first="Lorraine H." last="Keller">Lorraine H. Keller</name><affiliation wicri:level="2"><nlm:aff id="Aff2">MBF Therapeutics, Inc., 640 Woodbrook Drive, Ambler, PA 19002 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>MBF Therapeutics, Inc., 640 Woodbrook Drive, Ambler</wicri:cityArea></affiliation></author><author><name sortKey="Ertl, Hildegund C J" sort="Ertl, Hildegund C J" uniqKey="Ertl H" first="Hildegund C. J." last="Ertl">Hildegund C. J. Ertl</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><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</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>3601 Spruce Street, Philadelphia</wicri:cityArea></affiliation></author></analytic><series><title level="j">Cancer Immunology, Immunotherapy</title><idno type="ISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><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></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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uniqKey="Smedley R">RC Smedley</name></author><author><name sortKey="Lamoureux, J" uniqKey="Lamoureux J">J Lamoureux</name></author><author><name sortKey="Sledge, Dg" uniqKey="Sledge D">DG Sledge</name></author><author><name sortKey="Kiupel, M" uniqKey="Kiupel M">M Kiupel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montgomery, Ri" uniqKey="Montgomery R">RI Montgomery</name></author><author><name sortKey="Warner, Ms" uniqKey="Warner M">MS Warner</name></author><author><name sortKey="Lum, Bj" uniqKey="Lum B">BJ Lum</name></author><author><name sortKey="Spear, Pg" uniqKey="Spear P">PG Spear</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, G" uniqKey="Cai G">G Cai</name></author><author><name sortKey="Freeman, Gj" uniqKey="Freeman G">GJ Freeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stiles, Km" uniqKey="Stiles K">KM Stiles</name></author><author><name sortKey="Whitbeck, Jc" uniqKey="Whitbeck J">JC Whitbeck</name></author><author><name sortKey="Lou, H" uniqKey="Lou H">H Lou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lasaro, Mo" uniqKey="Lasaro M">MO Lasaro</name></author><author><name sortKey="Tatsis, N" uniqKey="Tatsis N">N Tatsis</name></author><author><name sortKey="Hensley, Se" uniqKey="Hensley S">SE Hensley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimenna, L" uniqKey="Dimenna L">L DiMenna</name></author><author><name sortKey="Latimer, B" uniqKey="Latimer B">B Latimer</name></author><author><name sortKey="Parzych, E" uniqKey="Parzych E">E Parzych</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahnke, Yd" uniqKey="Mahnke Y">YD Mahnke</name></author><author><name sortKey="Brodie, Tm" uniqKey="Brodie T">TM Brodie</name></author><author><name sortKey="Sallusto, F" uniqKey="Sallusto F">F Sallusto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pitcher, Cj" uniqKey="Pitcher C">CJ Pitcher</name></author><author><name sortKey="Hagen, Si" uniqKey="Hagen S">SI Hagen</name></author><author><name sortKey="Walker, Jm" uniqKey="Walker J">JM Walker</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Kurupati, Raj K" sort="Kurupati, Raj K" uniqKey="Kurupati R" first="Raj K." last="Kurupati">Raj K. Kurupati</name></region><name sortKey="Ertl, Hildegund C J" sort="Ertl, Hildegund C J" uniqKey="Ertl H" first="Hildegund C. J." last="Ertl">Hildegund C. J. Ertl</name><name sortKey="Keller, Lorraine H" sort="Keller, Lorraine H" uniqKey="Keller L" first="Lorraine H." last="Keller">Lorraine H. Keller</name><name sortKey="Xiang, Zhiquan" sort="Xiang, Zhiquan" uniqKey="Xiang Z" first="Zhiquan" last="Xiang">Zhiquan Xiang</name><name sortKey="Zhou, Xiangyang" sort="Zhou, Xiangyang" uniqKey="Zhou X" first="Xiangyang" last="Zhou">Xiangyang Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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