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.

NECTIN-4 PET FOR OPTIMIZING ENFORTUMAB VEDOTIN DOSE-RESPONSE IN UROTHELIAL CARCINOMA.

The optimization of dosing strategies is critical for maximizing efficacy and minimizing toxicity in drug development, particularly for drugs with narrow therapeutic windows such as antibody-drug conjugates (ADCs). This study demonstrates the utility of Nectin-4-targeted positron emission tomography (PET) imaging using [Ga]AJ647 as a non-invasive tool for real-time assessment of target engagement in enfortumab vedotin (EV) therapy for urothelial carcinoma (UC). By leveraging the specificity of [Ga]AJ647 for Nectin-4, we quantified dynamic changes in target engagement across preclinical models and established its correlation with therapeutic outcomes.

Microbiome-based Therapeutics: Cutting-edge Innovation or Perpetual Promise?

Recent preclinical and clinical research has established that the microbiome affects response to immunotherapy, and other work has shown that our diet has strong and rapid effects on the microbiome. Together, these findings have generated strong enthusiasm for the development of therapeutic approaches to exploit these effects. However, inconsistencies in sample collection and data analyses have made it challenging to evaluate the true impact of these interventions.

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).