# Evaluating Therapeutic Efficacy of Intravesical Xenogeneic Urothelial Cell Treatment Alone and in Combination with Chemotherapy or Immune Checkpoint Inhibition in a Mouse Non-Muscle-Invasive Bladder Cancer Model

## TL;DR

This study explores a new bladder cancer treatment using xenogeneic urothelial cells, showing promising results in delaying tumor growth and boosting immune responses in mice.

## Contribution

The study introduces a novel intravesical xenogeneic urothelial cell treatment for non-muscle-invasive bladder cancer.

## Key findings

- Intravesical XUC treatment significantly delayed tumor progression compared to the control group.
- Combined XUC treatment with chemotherapy or immune checkpoint inhibition showed higher antitumor effects than single treatments.
- XUC treatment activated immune responses, including immune cell proliferation and cytokine secretion.

## Abstract

The high recurrence rate and potential progression to muscle-invasive and metastatic stages have been great challenges for the management of high-risk non-muscle-invasive bladder cancer despite a variety of treatment options being available, including surgery, chemotherapy, and immunotherapy. To test a new immunotherapeutic approach to complement the current therapeutic modalities to achieve durable responses, we investigated the antitumor effect of a novel intravesical xenogeneic urothelial cell treatment in a murine non-muscle-invasive bladder cancer (NMIBC) model. Our study aimed to assess the potential use of this innovative therapeutic modality as a treatment option for NMIBC.

Background/Objectives: Bladder cancer is a malignant disease that causes more than 199,922 deaths a year globally, in which ~75% of all newly diagnosed cases are non-muscle-invasive bladder cancer (NMIBC). Despite a number of treatments available, most NMIBC patients with high-grade tumors eventually recur. To add a novel therapy to complement the deficits of the current treatments, this study assesses the antitumor activity and mechanisms of action of intravesical xenogeneic urothelial cell (XUC) treatment as monotherapy and in combination with either chemotherapy or immune checkpoint inhibition (ICI). Methods: The orthotopic NMIBC graft tumor-bearing mice were randomly assigned into different treatment groups, receiving either intravesical XUCs, gemcitabine, anti-programmed death-ligand 1 (PD-L1) antibodies alone or in combination with gemcitabine or anti-PD-1 antibodies. The tumor responses, survival, and immune reactions were analyzed. Results: Intravesical XUC treatment exhibited significantly more antitumor activity to delay tumor progression than the control group and a similar effect to chemotherapy and ICI. In addition, there were significantly higher effects in the combined groups than single treatments. Immune tumor microenvironment and immune cell proliferation, cytotoxicity, and cytokine secretion were also activated by XUC treatment. Moreover, the combined groups have the highest effects. Conclusions: In vivo and ex vivo studies showed increased antitumor efficacy and immune responses by intravesical XUC treatment in single and combined treatments, suggesting a potential utility of this xenogeneic cell immunotherapeutic agent. Intravesical XUC treatment has the potential to address the substantial unmet need in NMIBC therapy as a bladder-sparing treatment option for NMIBC.