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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...

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Autores principales: Ashton, Laura V., Weishaar, Kristen M., Séguin, Bernard, MacNeill, Amy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525839/
https://www.ncbi.nlm.nih.gov/pubmed/37760788
http://dx.doi.org/10.3390/biomedicines11092346
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author Ashton, Laura V.
Weishaar, Kristen M.
Séguin, Bernard
MacNeill, Amy L.
author_facet Ashton, Laura V.
Weishaar, Kristen M.
Séguin, Bernard
MacNeill, Amy L.
author_sort Ashton, Laura V.
collection PubMed
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.
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spelling pubmed-105258392023-09-28 Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma Ashton, Laura V. Weishaar, Kristen M. Séguin, Bernard MacNeill, Amy L. Biomedicines Article 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. MDPI 2023-08-23 /pmc/articles/PMC10525839/ /pubmed/37760788 http://dx.doi.org/10.3390/biomedicines11092346 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ashton, Laura V.
Weishaar, Kristen M.
Séguin, Bernard
MacNeill, Amy L.
Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525839/
https://www.ncbi.nlm.nih.gov/pubmed/37760788
http://dx.doi.org/10.3390/biomedicines11092346
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