title: γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria.
abstract: OBJECTIVE
  γ Irradiated Mycobacterium bovis bacillus Calmette-Guérin has shown in vitro and ex vivo antitumor activity. However, to our knowledge the potential antitumor capacity has not been demonstrated in vivo. We studied the in vivo potential of γ irradiated bacillus Calmette-Guérin and γ irradiated M. brumae, a saprophytic mycobacterium that was recently described as an immunotherapeutic agent.
  
  
  METHODS
  The antitumor capacity of γ irradiated M. brumae was first investigated by analyzing the in vitro inhibition of bladder tumor cell proliferation and the ex vivo cytotoxic effect of M. brumae activated peripheral blood cells. The effect of γ irradiated M. brumae or bacillus Calmette-Guérin intravesical treatment was then compared to treatment with live mycobacteria in the orthotopic murine model of bladder cancer.
  
  
  RESULTS
  Nonviable M. brumae showed a capacity to inhibit in vitro bladder cancer cell lines similar to that of live mycobacteria. However, its capacity to induce cytokine production was decreased compared to that of live M. brumae. γ Irradiated M. brumae could activate immune cells to inhibit tumor cell growth, although to a lesser extent than live mycobacteria. Finally, intravesical treatment with γ irradiated M. brumae or bacillus Calmette-Guérin significantly increased survival with respect to that of nontreated tumor bearing mice. Both γ irradiated mycobacteria showed lower survival rates than those of live mycobacteria but the minor efficacy of γ irradiated vs live mycobacteria was only significant for bacillus Calmette-Guérin.
  
  
  CONCLUSIONS
  Our results show that although γ irradiated mycobacteria is less efficacious than live mycobacteria, it induces an antitumor effect in vivo, avoiding the possibility of further mycobacterial infections.
authors.affiliation: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Noguera-Ortega
authors.affiliation: Unitat de Patologia Murina i Comparada, Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Rabanal
authors.affiliation: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Secanella-Fandos
authors.affiliation: Bacterial Infections and Antimicrobial Therapy Group, Institute for Bioengineering of Catalonia, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Torrents
authors.affiliation: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Luquin
authors.affiliation: Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: esther.julian@uab.cat.
authors.forename: Esther
authors.initials: E
authors.lastname: Julián
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D005260:Female; D005720:Gamma Rays; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000528:radiation effects*; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: BCG vaccine; Mycobacterium; gamma rays; immunotherapy; urinary bladder neoplasms