Insights on recent advances in immunotherapy of bladder cancer

Bladder cancer (BC) is a malignancy of the urinary system, characterized by a significant global incidence and prevalence. That involves high associated morbidity and mortality and different responses to therapy. Furthermore, there have been notable improvements in conventional treatment methods, including surgical interventions, chemotherapy, and the emergence of immunotherapy approaches. We conducted a non-systematic review using PubMed, Google Scholar, Scopus, Web of Science and American Association of Cancer Research (AACR) articles published from May ۲۰۱۵ to September ۲۰۲۴. Only articles written in English were considered. The array of authorized immunotherapeutic agents has significantly broadened, covering various preclinical and clinical applications within the field of cancer pharmacotherapy. Immunotherapy can also be effective in improving the clinical outcomes of patients with BC. The use of Bacillus Calmette-Guérin (BCG) immunotherapy in the last ۵۰ years has shown can be an effective treatment for high-grade non-muscle invasive bladder cancer (NMIBC). Neoadjuvant cisplatin-based multiagent chemotherapy is the standard of care for NMIBC. Immune checkpoint inhibitors (ICIs) are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Programmed Cell Death Protein ۱/Programmed Cell Death Ligand (PD-۱/PD-L۱) inhibitors (Atezolizumab, Pembrolizumab, Avelumab, Durvalumab, Nivolumab), Cytotoxic T-lymphocyte-associated protein ۴ (CTLA۴-۴) (Ipilimumab, Tremelimumab) and NKG۲A inhibitors (Monalizumab) were used. Immune checkpoint inhibitors are a therapeutic option that has been approved for all stages of BC and can improve the survival of patients with advanced stage. According to the AACR, the U.S Food and Drug Administration (FDA) has approved nogapendekin alfa inbakicept-pmln (NAI), in combination with BCG, for the treatment NMIBC. Based on results from the single-arm, multicenter, phase II/III QUILT-۳.۰۳۲ clinical trial, it can activate the IL-۱۵ receptor on the surface of some immune cells, including T cells and natural killer cells and increase their proliferation and activation. Other immunotherapeutic options available for BC are adaptive cell therapies, cytokine-based treatments, bispecific antibodies, and combinations of antibodies with drugs. Recent developments in immuno-oncology, particularly the integration of checkpoint inhibitors into the treatment protocols for various cancers, have significantly transformed the therapeutic landscape for urothelial cancer, a trend that is expected to persist. This paper aims to outline the historical background and foundational principles of immunotherapy in BC. Additionally, it will review the existing evidence regarding the efficacy of checkpoint inhibitors in this context, analyze ongoing clinical trials, and explore potential future developments in the treatment of BC. Furthermore, it will provide a thorough overview of both established and innovative immunotherapeutic agents that show potential for the management of BC.

کلیدواژه ها:

immunotherapy ، bladder cancer ، immune checkpoint inhibitor ، BCG ، PD-۱