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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
[Immunotherapy for Bladder Cancer]
Abstract:
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel. Studies of tumour microenvironment indicate a significant role for the immune system in the pathogenesis of urothelial tumours and the presence of a CD8 lymphocyte infiltrate is associated with better survival. In urothelial tumours, the correlation between PD-L1 expression in the tumour and the response to PD-1/PD-L1 inhibitors has been repeatedly demonstrated in clinical studies. Several inhibitors of PD-1/PD-L1 pathway are undergoing advanced-phase clinical trials and atezolizumab, nivolumab, pembrolizumab, durvalumab, and avelumab have already have received permanent or temporary registration status in the United States, mostly as second-line treatments for patients progressing on cisplatin-based chemotherapy. Three of these agents are currently registered in Europe: nivolumab for second line treatment and atezolizumab and pembrolizumab for first line treatment in patients not eligible for cisplatin as well as and for second line treatment. These novel immunotherapeutic agents for bladder cancer are relatively well tolerated and therefore potentially useful for patients with contraindications or intolerance to platinum regimens. The main toxicities include asthenia/fatigue, lymphopenia, anaemia, musculoskeletal pain, decreased appetite, and nausea.Key words: bladder cancer - imunotherapy - PD-1 receptor - antibodies - monoclonal This work was supported by the Czech Ministry of Health CR - RVO Thomayer Hospital - TN 0064190. The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 8. 2017Accepted: 3. 10. 2017.
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