Molecular profiling of bladder cancer xenografts defines relevant molecular subtypes and provides a resource for biomarker discovery.

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models.

Concomitant antihistamine administration is associated with improved survival outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with atezolizumab. Analysis of individual participant data from IMvigor210 and IMvigor211.

Objectives: Survival outcomes of patients with metastatic urothelial carcinoma (mUC) are still suboptimal and strategies to enhance response to immune-oncology (IO) compounds are under scrutiny. In preclinical studies, it has been demonstrated that antihistamines may reverse macrophage immunosuppression, reactivate T cell cytotoxicity, and enhance the immunotherapy response. We aimed to evaluate the role of concomitant antihistamines administration on oncological outcomes among patients with mUC.

Integrating gene therapy into the treatment paradigm for non-muscle invasive bladder cancer.

Introduction: Approximately 75% of bladder cancer cases are non-muscle invasive at diagnosis. Drug development for non-muscle invasive bladder cancer (NMIBC) has historically lagged behind that of other malignancies. No treatment has demonstrated the ability to overcome drug resistance that ultimately leads to recurrence and progression.

Single-cell RNA sequencing analysis identifies acute changes in the tumor microenvironment induced by interferon α gene therapy in a murine bladder cancer model.

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival.