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<p>Canine osteosarcoma (cOSA) and histiocytic sarcoma (cHS) are aggressive tumors characterized by poor prognoses and limited therapeutic options. Oncolytic viruses represent a promising treatment option for these tumors. Based on this hypothesis, this study aimed to evaluate direct and indirect oncolytic effects of Bovine Herpes virus type 1 (BoHV1) and a recombinant type 4 (BoHV4EGFPΔTK). Here we used cOSA, cHS and cutaneous fibroblast (FDOG) cell lines. BoHV1 and BoHV4EGFPΔTK can successfully infect cOSA and cHS cell lines with 1 multiplicity of infection (MOI). Notably, BoHV4EGFPΔTK displayed a less prominent ability to infect FDOG, whereas BoHV1 showed the highest percentage of infected cells in FDOG. Flow cytometry results showed that BoHV4EGFPΔTK, unlike BoHV1, induces a high percentage of dead and infected cells in all tumor cell lines. BoHV4EGFPΔTK infected FDOG showed over time a stable low percentage of dead and infected cells. Moreover, BoHV4EGFPΔTK infection of canine tumor cell lines triggered apoptosis and increased (Gasdermin-D) GSDM-D levels. Furthermore, both viruses exerted indirect oncolytic effects like influence on tumor cell motility. Efficacy varied by tumor cell line and time point. In conclusion, BoHV4EGFPΔTK compared to BoHV1, showed a prominent tropism for cancer cells and deserve future investigation to confirm its oncolytic potential.</p>

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Cross-species oncolytic virotherapy in vitro: BoHV4EGFPΔTK as a novel candidate against canine osteosarcoma and histiocytic sarcoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Di Pentima Melania,
  • Minesso Sergio,
  • Franceschi Valentina,
  • Di Lecce Rosanna,
  • Corradi Attilio,
  • Borghetti Paolo,
  • Donofrio Gaetano,
  • Razzuoli Elisabetta,
  • Fruscione Floriana,
  • Baumgärtner Wolfgang,
  • Vescovini Rosanna,
  • Andrani Melania,
  • Basini Giuseppina,
  • Bussolati Simona,
  • Passeri Benedetta,
  • Armando Federico

摘要

Canine osteosarcoma (cOSA) and histiocytic sarcoma (cHS) are aggressive tumors characterized by poor prognoses and limited therapeutic options. Oncolytic viruses represent a promising treatment option for these tumors. Based on this hypothesis, this study aimed to evaluate direct and indirect oncolytic effects of Bovine Herpes virus type 1 (BoHV1) and a recombinant type 4 (BoHV4EGFPΔTK). Here we used cOSA, cHS and cutaneous fibroblast (FDOG) cell lines. BoHV1 and BoHV4EGFPΔTK can successfully infect cOSA and cHS cell lines with 1 multiplicity of infection (MOI). Notably, BoHV4EGFPΔTK displayed a less prominent ability to infect FDOG, whereas BoHV1 showed the highest percentage of infected cells in FDOG. Flow cytometry results showed that BoHV4EGFPΔTK, unlike BoHV1, induces a high percentage of dead and infected cells in all tumor cell lines. BoHV4EGFPΔTK infected FDOG showed over time a stable low percentage of dead and infected cells. Moreover, BoHV4EGFPΔTK infection of canine tumor cell lines triggered apoptosis and increased (Gasdermin-D) GSDM-D levels. Furthermore, both viruses exerted indirect oncolytic effects like influence on tumor cell motility. Efficacy varied by tumor cell line and time point. In conclusion, BoHV4EGFPΔTK compared to BoHV1, showed a prominent tropism for cancer cells and deserve future investigation to confirm its oncolytic potential.