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Background <p>Recombinant Bacillus Calmette-Guérin (rBCG) is a genetically modified BCG that enhances therapeutic efficacy and safety in patients with bladder cancer. Pembrolizumab is an immune checkpoint inhibitor (ICI) that is used to treat bladder cancer. We aimed to evaluate the effectiveness of the combination of rBCG and pembrolizumab in vitro and in vivo bladder cancer models.</p> Methods <p>We investigated the antitumor effects of rBCG-<i>dltA</i> and pembrolizumab in a bladder cancer-on-a-chip (BCOC) model, an organoid three-dimensional cell culture tool. An orthotopic mouse model was employed to assess the in vivo effects of the combination therapy. To overcome limitations arising from differences between species, an in vivo study was conducted using a mouse PD-1 inhibitor instead of pembrolizumab.</p> Results <p>The T24 bladder cancer cell line showed reduced viability when rBCG-<i>dltA</i> and pembrolizumab were used in the BCOC model. Monocyte migration was also significantly greater than that in the other groups. In the orthotopic bladder cancer model, the combination treatment inhibited the growth of bladder cancer.</p> Conclusions <p>Intravesical therapy with rBCG-<i>dltA</i> and pembrolizumab may be effective in treating bladder cancer. This study suggests that the combination of rBCG and ICIs may be an alternative strategy for treating patients with BCG-unresponsive bladder cancer.</p>

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The potential antitumor effects of combining intravesical therapy with recombinant bacillus calmette-guérin and an anti-PD-1 inhibitor in bladder cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月29日

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  • Jung Hoon Kim,
  • Sejung Maeng,
  • Joongwon Choi,
  • Chung Un Lee,
  • Yong Seong Lee,
  • Mirinae Kim,
  • Se Young Choi,
  • In Ho Chang

摘要

Background

Recombinant Bacillus Calmette-Guérin (rBCG) is a genetically modified BCG that enhances therapeutic efficacy and safety in patients with bladder cancer. Pembrolizumab is an immune checkpoint inhibitor (ICI) that is used to treat bladder cancer. We aimed to evaluate the effectiveness of the combination of rBCG and pembrolizumab in vitro and in vivo bladder cancer models.

Methods

We investigated the antitumor effects of rBCG-dltA and pembrolizumab in a bladder cancer-on-a-chip (BCOC) model, an organoid three-dimensional cell culture tool. An orthotopic mouse model was employed to assess the in vivo effects of the combination therapy. To overcome limitations arising from differences between species, an in vivo study was conducted using a mouse PD-1 inhibitor instead of pembrolizumab.

Results

The T24 bladder cancer cell line showed reduced viability when rBCG-dltA and pembrolizumab were used in the BCOC model. Monocyte migration was also significantly greater than that in the other groups. In the orthotopic bladder cancer model, the combination treatment inhibited the growth of bladder cancer.

Conclusions

Intravesical therapy with rBCG-dltA and pembrolizumab may be effective in treating bladder cancer. This study suggests that the combination of rBCG and ICIs may be an alternative strategy for treating patients with BCG-unresponsive bladder cancer.