Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma
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) co...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/9/2346 |
| _version_ | 1827727103759482880 |
|---|---|
| author | Laura V. Ashton Kristen M. Weishaar Bernard Séguin Amy L. MacNeill |
| author_facet | Laura V. Ashton Kristen M. Weishaar Bernard Séguin Amy L. MacNeill |
| author_sort | Laura V. Ashton |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T23:01:49Z |
| format | Article |
| id | doaj.art-c755e898e10b48bc94ea779f2da7a1f9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:01:49Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-c755e898e10b48bc94ea779f2da7a1f92023-11-19T09:40:01ZengMDPI AGBiomedicines2227-90592023-08-01119234610.3390/biomedicines11092346Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue SarcomaLaura V. Ashton0Kristen M. Weishaar1Bernard Séguin2Amy L. MacNeill3Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USAClinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USACentral Victoria Veterinary Hospital, Victoria, BC V8X 2R3, CanadaMicrobiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USAHuman 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.https://www.mdpi.com/2227-9059/11/9/2346cytokinesoclacitiniboncolytic virusdogscancer |
| spellingShingle | Laura V. Ashton Kristen M. Weishaar Bernard Séguin Amy L. MacNeill Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma Biomedicines cytokines oclacitinib oncolytic virus dogs cancer |
| title | Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma |
| title_full | Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma |
| title_fullStr | Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma |
| title_full_unstemmed | Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma |
| title_short | Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma |
| title_sort | oclacitinib and myxoma virus therapy in dogs with high grade soft tissue sarcoma |
| topic | cytokines oclacitinib oncolytic virus dogs cancer |
| url | https://www.mdpi.com/2227-9059/11/9/2346 |
| work_keys_str_mv | AT lauravashton oclacitinibandmyxomavirustherapyindogswithhighgradesofttissuesarcoma AT kristenmweishaar oclacitinibandmyxomavirustherapyindogswithhighgradesofttissuesarcoma AT bernardseguin oclacitinibandmyxomavirustherapyindogswithhighgradesofttissuesarcoma AT amylmacneill oclacitinibandmyxomavirustherapyindogswithhighgradesofttissuesarcoma |