Bacillus Calmette–Guérin (BCG) immunotherapy is the gold standard for nonmuscle invasive bladder cancer (NMIBC). However, it is limited by adverse effects and resistance, despite eliciting a robust immune response. This proof-of-concept study explores Antigen 85-mediated, metabolically with trehalose-PEG₄ mertansine-labeled BCG as a novel treatment option for NMIBC, offering promising in cellulo results.

Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancer cases, with Bacillus Calmette–Guérin (BCG) immunotherapy as the gold standard for high-risk patients. BCG elicits a robust immune response but is limited by adverse effects and resistance. To enhance its efficacy, a trehalose-based conjugation strategy is developed, tethering a cytostatic agent to BCG via a cleavable disulfide linker. This system enables selective drug integration into the BCG envelope and controlled release in tumor cells, aiming to improve therapeutic precision while minimizing toxicity. This approach combines immunotherapy with targeted chemotherapy, offering a promising strategy for NMIBC treatment.