Oncolytic virotherapy provides a potent therapy option for squamous bladder cancer
Abstract Prognosis for squamous cell carcinoma (SCC) of the bladder is limited mostly because of lack of effective treatment regimens. Oncolytic virotherapy represents a promising option for bladder cancer and received in 2024 FDA therapy designation for the treatment of non-invasive high-grade blad...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-96419-3 |
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| Summary: | Abstract Prognosis for squamous cell carcinoma (SCC) of the bladder is limited mostly because of lack of effective treatment regimens. Oncolytic virotherapy represents a promising option for bladder cancer and received in 2024 FDA therapy designation for the treatment of non-invasive high-grade bladder cancer (BLCA). For muscle-invasive bladder cancer (MIBC), preclinical studies demonstrated high efficacy of the oncolytic adenovirus XVir-N-31 in urothelial carcinoma (UC). We analyzed the potency of XVir-N-31 virotherapy as a novel treatment option in SCC. Replication of XVir-N-31 has been described to be facilitated by high expression level of Y-Box binding protein 1 (YB-1). Increased YB-1-mRNA expression was detected in basal/squamous subtype in TCGA BLCA cohort compared to urothelial and luminal BLCA and correlated with patient outcomes. Furthermore, immunohistochemical staining of 89 SCC on a tissue microarray confirmed strong YB-1 expression in squamous BLCA (sq-BLCA). In vitro, XVir-N-31 showed in subtype-specific cell cultures high rates of infection, replication and cell-killing capacity. In a novel in ovo xenograft model, XVir-N-31 impaired growth of xenografts of patient-derived ex vivo cell lines (p-SCC, p-UC) with growth suppression rates of 39–49%. We provide preclinical evidence ex vivo and in ovo for high efficacy of XVir-N-31 based oncolytic virotherapy as novel SCC therapy. |
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| ISSN: | 2045-2322 |