Recombinant bacillus Calmette-Guérin in urothelial bladder cancer immunotherapy: current strategies

Abstract

Bacillus Calmette-Guérin (BCG) has been used in the intravesical treatment of urothelial bladder cancer (UBC) for three decades. Despite its efficacy, intravesical BCG therapy is associated with some limitations such as side effects and BCG failure, which have inspired multiple ways to improve it. Recent advances have focused on recombinant BCG (rBCG) which provides a novel tactic for modification of BCG. To date, a number of rBCG strains have been developed and demonstrated to encourage efficacy and safety in preclinical and clinical studies. This review summarizes current rBCG strategies, concerns and future directions in UBC immunotherapy with an intention to encourage further research and eventually to inform clinical decisions.

Keywords:

• bacillus Calmette-Guérin
• BCG
• immunotherapy
• intravesical therapy
• recombinant BCG
• urothelial bladder cancer

Financial & competing interests disclosure

This work was supported by National Natural Science Foundation of China (No. 81101932). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Intravesical bacillus Calmette–Guérin (BCG) therapy is still the most common therapy used for non-muscle invasive bladder cancer, but associated with some limitations such as side effects and BCG failure.

• Recombinant BCG (rBCG) strategies represent a major advance in the modification of BCG therapy in recent years. Various rBCG strains have been developed and demonstrated to encourage efficacy and safety in preclinical and clinical studies.

• Th1 cytokine-based rBCG strains have the advantage of inducing enhanced efficacy from specific expressing cytokines and may benefit patients with BCG failure.

• BCG subcomponent-based rBCG strains have the same immunogenicity but lower toxicity compared to live BCG and may be more suitable for patients who cannot tolerate the side effects of BCG.

• There are still some unanswered questions regarding the application of rBCG strategies. Further researches are warranted to determine credible clinical efficacy and safety, suitable patients, optimal dose and treatment schedule of rBCG strategies.

• Some new candidates such as MUC1 and soluble PD-1 may have potential prospect and need much more investigation.