Bladder Cancer Medication Bacillus Calmette-Guérin-Cell Wall Skeleton Focusing on Alternatives and Developments to Limitations.

Abstract

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug. To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.