Therapeutic efficacy of the live-attenuated Mycobacterium tuberculosis vaccine, MTBVAC, in a preclinical model of bladder cancer

Alvarez-Arguedas, S. ; Uranga, S. (Universidad de Zaragoza) ; Martín, M. ; Elizalde, J. ; Gomez, A.B. (Universidad de Zaragoza) ; Julián, E. ; Nardelli-Haefliger, D. ; Martín, C. (Universidad de Zaragoza) ; Aguilo, N. (Universidad de Zaragoza)

Resumen: Intravesical instillation of bacillus Calmette-Guérin (BCG) has been a first-line therapy for non–muscle-invasive bladder cancer for the last 4 decades. However, this treatment causes serious adverse events in a significant number of patients and a substantial percentage of recurrence episodes. MTBVAC is a live-attenuated vaccine derived from a Mycobacterium tuberculosis clinical isolate and is currently under evaluation in clinical trials to replace BCG as a tuberculosis vaccine. Here, we describe for the first time the potential of MTBVAC as a bladder cancer therapy in vitro and in vivo in a preclinical model. MTBVAC colonized human bladder tumor cells to a much greater extent than BCG via a mechanism mediated by macropinocytosis and induced cell growth inhibition after internalization. In vivo testing in an orthotopic murine model of bladder cancer demonstrated a higher antitumor effect of MTBVAC in experimental conditions in which BCG did not work. Our data encourage further studies to support the possible application of MTBVAC as a new immunotherapeutic agent for bladder cancer.

Idioma: Inglés

DOI: 10.1016/j.trsl.2018.03.004

Año: 2018

Publicado en: Translational Research 197 (2018), 32-42
ISSN: 1931-5244

Factor impacto JCR: 4.915 (2018)

Categ. JCR: MEDICAL LABORATORY TECHNOLOGY rank: 2 / 29 = 0.069 (2018) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 22 / 135 = 0.163 (2018) - Q1 - T1
Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 19 / 159 = 0.119 (2018) - Q1 - T1

Factor impacto SCIMAGO: 1.803 - Biochemistry (medical) (Q1) - Public Health, Environmental and Occupational Health (Q1) - Physiology (medical) (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/FSE
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)