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Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma

Synovial sarcoma (SS) is a pediatric muscle cancer that primarily affects adolescents and young adults and has few treatment options. Complicating the treatment of synovial sarcoma is the low mutational burden of SS. Inflammatory pathways have been identified as being upregulated in some SS, leading...

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Autores principales: McCollum, Sarah, Kalivas, Austen, Kirkham, Matthew, Kunz, Kaden, Okojie, Jeffrey, Pavek, Adriene, Barrott, Jared
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228444/
https://www.ncbi.nlm.nih.gov/pubmed/35745569
http://dx.doi.org/10.3390/ph15060650
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author McCollum, Sarah
Kalivas, Austen
Kirkham, Matthew
Kunz, Kaden
Okojie, Jeffrey
Pavek, Adriene
Barrott, Jared
author_facet McCollum, Sarah
Kalivas, Austen
Kirkham, Matthew
Kunz, Kaden
Okojie, Jeffrey
Pavek, Adriene
Barrott, Jared
author_sort McCollum, Sarah
collection PubMed
description Synovial sarcoma (SS) is a pediatric muscle cancer that primarily affects adolescents and young adults and has few treatment options. Complicating the treatment of synovial sarcoma is the low mutational burden of SS. Inflammatory pathways have been identified as being upregulated in some SS, leading to the discovery of upregulated oncostatin M receptor (OSMR). It was found that OSMR is upregulated in SS by RNAseq analysis and quantitative PCR, highlighting its potential in the treatment of SS. Also, OSMR is upregulated in mouse models for synovial sarcoma as demonstrated by western blot and immunohistochemistry, and the protein is present in both primary and metastatic sites of disease. Using a radioimmune therapy drug model, targeted therapy was synthesized for use in OSMR expressing SS and it was demonstrated that this drug is stable, while capable of efficient OSMR binding and isotope capture. Finally, this antibody conjugate exhibited ideal pharmacokinetics and targeted sites of disease in our mouse model and was taken up in both primary and metastatic diseased tissue. This suggests OSMR as an ideal target for therapy and this radioimmune therapy provides a novel treatment option for a disease with few therapy choices.
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spelling pubmed-92284442022-06-25 Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma McCollum, Sarah Kalivas, Austen Kirkham, Matthew Kunz, Kaden Okojie, Jeffrey Pavek, Adriene Barrott, Jared Pharmaceuticals (Basel) Article Synovial sarcoma (SS) is a pediatric muscle cancer that primarily affects adolescents and young adults and has few treatment options. Complicating the treatment of synovial sarcoma is the low mutational burden of SS. Inflammatory pathways have been identified as being upregulated in some SS, leading to the discovery of upregulated oncostatin M receptor (OSMR). It was found that OSMR is upregulated in SS by RNAseq analysis and quantitative PCR, highlighting its potential in the treatment of SS. Also, OSMR is upregulated in mouse models for synovial sarcoma as demonstrated by western blot and immunohistochemistry, and the protein is present in both primary and metastatic sites of disease. Using a radioimmune therapy drug model, targeted therapy was synthesized for use in OSMR expressing SS and it was demonstrated that this drug is stable, while capable of efficient OSMR binding and isotope capture. Finally, this antibody conjugate exhibited ideal pharmacokinetics and targeted sites of disease in our mouse model and was taken up in both primary and metastatic diseased tissue. This suggests OSMR as an ideal target for therapy and this radioimmune therapy provides a novel treatment option for a disease with few therapy choices. MDPI 2022-05-24 /pmc/articles/PMC9228444/ /pubmed/35745569 http://dx.doi.org/10.3390/ph15060650 Text en © 2022 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
McCollum, Sarah
Kalivas, Austen
Kirkham, Matthew
Kunz, Kaden
Okojie, Jeffrey
Pavek, Adriene
Barrott, Jared
Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title_full Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title_fullStr Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title_full_unstemmed Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title_short Oncostatin M Receptor as a Therapeutic Target for Radioimmune Therapy in Synovial Sarcoma
title_sort oncostatin m receptor as a therapeutic target for radioimmune therapy in synovial sarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228444/
https://www.ncbi.nlm.nih.gov/pubmed/35745569
http://dx.doi.org/10.3390/ph15060650
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