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Abstract 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.
Kim et al. (2026) studied this question.