# Targeting Bladder Cancer with Inactivated Uropathogenic E. coli: A Novel Alternative to BCG Immunotherapy

## TL;DR

Researchers tested inactivated uropathogenic E. coli as a safer and more effective alternative to BCG for bladder cancer treatment, showing promising results in animal models.

## Contribution

The study introduces inactivated UPEC as a novel, tumor-targeting immunotherapeutic agent with a better safety profile than BCG.

## Key findings

- Intravesical administration of inactivated UPEC reduced tumor burden and prolonged survival in bladder cancer models.
- The antitumor effect of UPEC is T cell-dependent and partially mediated by type I fimbriae.
- Systemic administration of UPEC was ineffective and increased mortality, highlighting the need for localized delivery.

## Abstract

More than 90% of bladder cancers are classified as urothelial carcinomas (UC), with approximately 75% of these cases presenting as non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette–Guérin (BCG) is the current standard immunotherapy for NMIBC, yet it suffers from limited efficacy, frequent tumor recurrence, and substantial toxicity. These limitations underscore the need for safer, more effective, and accessible alternatives. We investigated whether uropathogenic Escherichia coli (UPEC), a natural inducer of immune responses in the bladder, could serve as a novel intravesical immunotherapeutic agent. Using orthotopic bladder cancer models in both mice (MB49-luc) and rats (AY-27), we evaluated the efficacy, specificity, immune dependence, and safety of formaldehyde-inactivated UPEC strains, including mutants with altered type 1 fimbriae expression. Intravesical administration of inactivated UPEC significantly reduced tumor burden and prolonged survival, outperforming BCG in murine models and demonstrating equivalent efficacy with markedly reduced toxicity in rats. The antitumor effect was T cell-dependent and partially mediated by type I fimbriae, which facilitated tumor-specific adhesion. Notably, systemic (subcutaneous) administration of UPEC abrogated efficacy and increased mortality, emphasizing the necessity of localized bladder delivery. In conclusion, we identify inactivated UPEC as a potent, tumor-targeting, and T cell-dependent immunotherapeutic agent with a superior safety profile compared to BCG. This approach might represent a promising and practical alternative for bladder cancer treatment.