Neo-Adjuvant immunotherapies: Bladder cancer as a platform for drug development targeting mucosal immunity.
Eur J Cancer
; 187: 58-64, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-37116288
ABSTRACT
Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium bovis strain, originally developed as a vaccine against tuberculosis. It is also the only bacterial cancer therapy approved by the US Food & Drug Administration for clinical use. BCG is delivered in the bladder, shortly after tumour resection, for patients with high-risk non-muscle invasive bladder cancer (NMIBC). Modulating mucosal immunity by exposing the urothelium to intravesical BCG has been the main therapeutic strategy for high-risk NMIBC over the last three decades. Thus, BCG provides a benchmark for the clinical development of bacteria-or other live attenuated pathogens-as cancer therapy. Currently, a myriad of immuno-oncology compounds is under clinical evaluation in BCG-unresponsive and BCG-naïve patients as an alternative therapy in the context of worldwide BCG shortages. For patients with non-metastatic muscle-invasive bladder cancer (MIBC), studies investigating neoadjuvant immunotherapy with either anti-PD-1/PD-L1 monoclonal antibodies in monotherapy or in combination with anti-CTLA-4 monoclonal antibodies have shown overall efficacy and acceptable safety profiles prior to radical cystectomy. Emerging clinical investigations are testing synergistic approaches by combining intravesical delivery of drugs with systemic immune checkpoint blockades in the neoadjuvant setting for patients with MIBC. Such novel strategy aims to prime a local anti-tumour immunity and reduce distant metastatic relapses by enhancing a systemic adaptive anti-tumour immune response. Here, we present and discuss some of the most promising clinical trials developing such novel therapeutic approaches.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Vacina BCG
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França