Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
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) g, tumor necrosis factor (TNF) a, 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.
Cancer Immunology, Immunotherapy