The Potential Antitumor Effects of Combining Intravesical Therapy with Recombinant Bacillus Calmette-Guérin and an Immune Checkpoint Inhibitor in Bladder Cancer

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 that is used to treat bladder cancer. We aimed to evaluate the effectiveness of the combination of rBCG and pembrolizumab in 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 errors caused by differences between species, an in vivo study was conducted using a mouse PD1 inhibitor instead of pembrolizumab. Results The T24 bladder cancer cell line declined independently 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 is effective in treating bladder cancer. This study suggests that the combination of rBCG and immune checkpoint inhibitors is a novel strategy for treating patients with BCG-unresponsive bladder cancer.