The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA.
MBF Therapeutics, Inc., 640 Woodbrook Drive, Ambler, PA, 19002, USA.
Cancer Immunol Immunother. 2018 Oct;67(10):1533-1544. doi: 10.1007/s00262-018-2201-5. Epub 2018 Jul 26.
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.
近年来，人类免疫疗法中的检查点阻断已取得重大突破。在这项研究中，我们测试了一种用于犬黑色素瘤的检查点阻断疫苗的安全性和免疫原性。 5 只健康成年犬接受了三种复制缺陷型黑猩猩衍生腺病毒载体的混合物的治疗，其中一种表达小鼠成纤维细胞相关蛋白（mFAP），其他两种则表达与犬黑色素瘤相关的抗原 Trp-1 或 Trp-2，与单纯疱疹病毒进入介体（HVEM）途径的检查点抑制剂融合。结果表明，疫苗混合物具有良好的耐受性，并分别在四只和五只犬中增加了犬 Trp-1 特异性激活的 CD8 和 CD4 T 细胞的频率，这些细胞单独或组合分泌干扰素-（IFN）-γ、肿瘤坏死因子（TNF）-α 或白细胞介素（IL）-2。为了避免过度出血，未分析对 cTrp-2 的反应。所有犬均对 mFAP 特异性激活的 CD8 和 CD4 T 细胞的频率增加做出了反应。这项安全性/免疫原性试验的结果，邀请了进一步在患有黑色素瘤的犬中测试这种检查点阻断疫苗组合。
