Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
Identifieur interne : 000804 ( Ncbi/Curation ); précédent : 000803; suivant : 000805Safety 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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PMC:7080056Le document en format XML
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<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>
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