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<p>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 <i>YB-1</i>-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). <i>In vitro</i>, XVir-N-31 showed in subtype-specific cell cultures high rates of infection, replication and cell-killing capacity. In a novel <i>in ovo</i> xenograft model, XVir-N-31 impaired growth of xenografts of patient-derived <i>ex vivo</i> cell lines (p-SCC, p-UC) with growth suppression rates of 39–49%. We provide preclinical evidence <i>ex vivo</i> and <i>in ovo</i> for high efficacy of XVir-N-31 based oncolytic virotherapy as novel SCC therapy.</p>

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Oncolytic virotherapy provides a potent therapy option for squamous bladder cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月18日

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  • Julia Pannhausen,
  • Julia Wirtz,
  • Klaus Mantwill,
  • Per-Sonne Holm,
  • Kristina Schwamborn,
  • Danny D. Jonigk,
  • Jürgen E. Gschwend,
  • Michael Rose,
  • Nadine T. Gaisa,
  • Roman Nawroth

摘要

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.