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

Pharmaceuticals

Sarah McCollum¹  Jeffrey Okojie¹  Matthew Kirkham¹  Austen Kalivas¹  Kaden Kunz¹  Jared Barrott¹  Adriene Pavek¹ 

[1] Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA;

关键词: synovial sarcoma;    sarcoma;    oncology;    radioimmune therapy;    RIT;    OSMR;   

DOI  :  10.3390/ph15060650

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown