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Bacillus Calmette-Guérin (BCG) associated antigens are a complex group of immunogenic molecules, including proteins like the Antigen 85 complex and cell wall components like mycolic acids, derived from the attenuated Mycobacterium bovis strain (StatPearls, 2023). These antigens are the functional components of the BCG vaccine, which has been used for over a century to prevent tuberculosis by priming the immune system to recognize similar antigens in Mycobacterium tuberculosis (WHO, 2023). In oncology, these antigens are the basis for intravesical BCG immunotherapy, the standard of care for high-risk non-muscle invasive bladder cancer (NIH/NCI, 2024). Upon administration, the antigens stimulate a profound local inflammatory response in the bladder, characterized by the activation of Toll-like receptors and the recruitment of various immune effectors that target malignant cells (Redelman-Sidi et al., 2014). This response involves the activation of the urothelium and the recruitment of various immune cells, such as macrophages and T cells, which collectively target and destroy malignant cells (Fuge et al., 2015). Despite its efficacy, the use of these antigens is associated with risks such as systemic BCG infection and severe local side effects, necessitating careful patient selection and monitoring (CDC, 2023).
Induction of a Th1-polarized immune response through the activation of Toll-like receptors (TLR2 and TLR4) on urothelial and immune cells, leading to the secretion of pro-inflammatory cytokines (IFN-gamma, IL-12) and the recruitment of cytotoxic T lymphocytes and natural killer cells to the site of administration (Redelman-Sidi et al., 2014; Fuge et al., 2015).
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