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Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma
Laura V Ashton1, Kristen M Weishaar2, Bernard Séguin3
1Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Abstract:
Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high-grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and human cancer patients. To develop an appropriate combination of immunotherapy and OV for dogs with soft tissue sarcoma (STS), canine cancer cells were inoculated with myxoma viruses (MYXVs) and gene transcripts were quantified. Next, the cytokine concentrations in the canine cancer cells were altered to evaluate their effect on MYXV replication. These studies indicated that, as in murine and human cells, type I interferons (IFN) play an important role in limiting MYXV replication in canine cancer cells. To reduce type I IFN production during OV, oclacitinib (a JAK1 inhibitor) was administered twice daily to dogs for 14 days starting ~7 days prior to surgery. STS tumors were excised, and MYXV deleted for serp2 (MYXV∆SERP2) was administered at the surgical site at two time points post-operatively to treat any remaining microscopic tumor cells. Tumor regrowth in dogs treated with OV was decreased relative to historical controls. However, regrowth was not further inhibited in patients given combination therapy.
Insights
Combining oncolytic virotherapy (OV) with immunotherapy showed promise in treating canine soft tissue sarcoma (STS). While OV alone reduced tumor regrowth, the combination therapy did not yield further benefits in this study.
Area of Science:
- Veterinary Oncology
- Immunotherapy
- Oncolytic Virotherapy
Background:
- Soft tissue sarcomas (STS) in dogs share similarities with human rhabdomyosarcomas, making canine models valuable for cancer therapy research.
- Combining oncolytic virotherapy (OV) with immunotherapy offers potential for improved cancer treatment outcomes in both canine and human patients.
Purpose of the Study:
- To investigate the efficacy of combining OV with immunotherapy for treating canine soft tissue sarcoma (STS).
- To evaluate the role of type I interferons (IFN) in limiting myxoma virus (MYXV) replication in canine cancer cells and explore strategies to mitigate this effect.
Main Methods:
- Canine cancer cells were infected with myxoma viruses (MYXVs) to analyze gene transcripts and cytokine concentrations.
- Oclacitinib, a JAK1 inhibitor, was administered to dogs to reduce type I IFN production prior to surgical excision of STS tumors.
- Post-operatively, MYXV deleted for serp2 (MYXV∆SERP2) was administered at the surgical site to target residual microscopic tumor cells.
Main Results:
- Myxoma virus (MYXV) replication in canine cancer cells was found to be limited by type I interferons (IFN), similar to murine and human cells.
- Tumor regrowth was decreased in dogs treated with OV compared to historical controls.
- Combination therapy, including immunotherapy and OV, did not demonstrate further inhibition of tumor regrowth compared to OV alone.
Conclusions:
- Oncolytic virotherapy (OV) alone showed a positive effect in reducing tumor regrowth in canine soft tissue sarcoma (STS).
- The combination of OV with immunotherapy, specifically using oclacitinib to inhibit type I IFN, did not enhance therapeutic outcomes in this study.
- Further research is needed to optimize combination strategies for canine and human cancer therapies involving OV and immunotherapy.
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