# rBCG-LTAK63 Outperforms BCG in Bladder Cancer Immunotherapy: Dendritic and T Cell Coordination Drives Superior Tumor Control in a Mouse Model

## TL;DR

A new version of BCG, called rBCG-LTAK63, shows better results than standard BCG in treating bladder cancer by boosting immune cell activity in mice.

## Contribution

rBCG-LTAK63 is a novel recombinant BCG strain that enhances immune responses and tumor control in bladder cancer models.

## Key findings

- rBCG-LTAK63 outperforms BCG in activating T cells and controlling tumor growth in vitro and in vivo.
- rBCG-LTAK63 promotes stronger activation of dendritic cells, NK cells, and effector T cells while reducing regulatory T cells in the tumor microenvironment.
- The improved immunostimulatory profile of rBCG-LTAK63 suggests translational potential for non-muscle invasive bladder cancer treatment.

## Abstract

Bacillus Calmette-Guérin (BCG) remains the standard treatment for non-muscle invasive bladder cancer (NMIBC), yet approximately 30% of patients fail to respond. To enhance therapeutic efficacy, we developed rBCG-LTAK63, a recombinant BCG strain, as a novel immunotherapeutic candidate. In vitro, rBCG outperformed BCG in MB49 cell/splenocyte co-cultures by enhancing T cell activation and improving spheroid growth control. In vivo, rBCG demonstrated superior antitumor efficacy, significantly reducing the growth of subcutaneously implanted MB49 tumor cells. Immune profiling revealed that rBCG uniquely promoted systemic activation of both CD4⁺ and CD8⁺ T cells, alongside stronger activation of NK and dendritic cells in the spleen. Within the tumor microenvironment, rBCG increased immune cell infiltration, enhanced activation of CD8⁺ T cells and dendritic cells, and decreased the frequency of regulatory T cells, fostering a less immunosuppressive environment. Unlike parental BCG, rBCG-LTAK63 sustained a potent immunostimulatory profile, marked by robust activation of dendritic cells and effector T cells. Similar results were also observed in the orthotopic model, suggesting a translational potential of rBCG-LTAK63. Collectively, our findings demonstrate that rBCG outperforms conventional BCG and represents a promising strategy for improving NMIBC treatment.