Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer
2016; Landes Bioscience; Volume: 6; Issue: 1 Linguagem: Inglês
10.1080/2162402x.2016.1265720
ISSN2162-402X
AutoresSonia Domingos‐Pereira, Valérie Cesson, Mathieu F. Chevalier, Laurent Derré, Patrice Jichlinski, Denise Nardelli‐Haefliger,
Tópico(s)Cancer Research and Treatments
ResumoIntravesical Bacillus-Calmette-Guérin (BCG) immunotherapy can reduce recurrence/progression of non-muscle-invasive bladder cancer (NMIBC), although significant adverse events and treatment failure argue for alternative options. Here, we examined whether another attenuated live vaccine, Vivotif/Ty21a, used since more than 30 y against typhoid fever, may be safely used intravesically to improve bladder-tumor treatment. Mice-bearing MB49 orthotopic bladder-tumors treated with intravesical Ty21a or BCG were compared for survival and bacteria recovery. Both Ty21a and BCG enhanced mice survival when treating just after tumor implantation for 4 weeks (p = 0.008 and 0.04, respectively), but only Ty21a was effective when treating once mice with larger already established bladder-tumors (p = 0.0003). In contrast to BCG, no Ty21a bacteria survived in mouse bladder, human urothelial cell-lines or human peripheral blood mononuclear cells. However, Ty21a was as potent as BCG to induce tumor-cell death in vitro. In a human, 3D-bladder-tissue ex-vivo assay, Ty21a bacteria, still not surviving, induced a panel of cytokines associated with effective BCG-treatment in patient's urine. Overall, our pre-clinical data demonstrate that intravesical Ty21a is more effective than BCG for bladder-tumor treatment. Absence of surviving Ty21a bacteria and the excellent safety-record of the typhoid vaccine support its testing in NMIBC patients.
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