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

Area of Science:

• Veterinary Oncology
• Virology
• Cancer Therapeutics

Background:

• Canine osteosarcoma (cOSA) and histiocytic sarcoma (cHS) are aggressive cancers with poor prognoses.
• Oncolytic viruses offer a potential new therapeutic avenue for these canine tumors.

Purpose of the Study:

• To evaluate the direct and indirect oncolytic effects of Bovine Herpesvirus type 1 (BoHV1) and a recombinant Bovine Herpesvirus type 4 (BoHV4EGFPΔTK).
• To assess the efficacy of these viruses against canine tumor cell lines and normal canine fibroblasts.

Main Methods:

• Infection of canine osteosarcoma (cOSA), canine histiocytic sarcoma (cHS), and canine fibroblast (FDOG) cell lines with BoHV1 and BoHV4EGFPΔTK at a multiplicity of infection (MOI) of 1.
• Flow cytometry analysis to quantify infected and dead cells.
• Assessment of apoptosis and Gasdermin-D (GSDM-D) levels.
• Evaluation of indirect oncolytic effects, such as tumor cell motility.

Main Results:

• Both BoHV1 and BoHV4EGFPΔTK infected cOSA and cHS cells.
• BoHV4EGFPΔTK demonstrated greater specificity, infecting fewer normal canine fibroblasts (FDOG) compared to BoHV1.
• BoHV4EGFPΔTK induced significant cell death and apoptosis in tumor cell lines, with minimal impact on FDOG cells over time.
• Both viruses exhibited indirect oncolytic effects, influencing tumor cell motility.

Conclusions:

• BoHV4EGFPΔTK exhibits promising cancer cell tropism and oncolytic potential against canine sarcomas compared to BoHV1.
• Further investigation is warranted to confirm the therapeutic efficacy of BoHV4EGFPΔTK for canine cancer treatment.