PURPOSE: Evolutionarily early and late bacillus Calmette-Guérin substrains are genetically distinct, showing different antigenic determinants. While it was suggested that this may influence the immunostimulatory effects of bacillus Calmette-Guérin as a vaccine in the context of tuberculosis, to our knowledge the impact of these genetic differences on the antitumor activity of bacillus Calmette-Guérin remains unknown. We compared the direct antitumor capacity and the ability to trigger cytokine production of 8 evolutionarily early and late BCG substrains in urothelial bladder cancer cell lines. MATERIALS AND METHODS: The T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of 3 evolutionarily early bacillus Calmette-Guérin substrains (Japan, Moreau and Russian) and 5 evolutionarily late strains (Connaught, Danish, Glaxo, Phipps and Tice). The inhibition of cell proliferation at different time points and the production of interleukin-6 and 8 in cell culture supernatants were measured. RESULTS: For T24 and J82 cells Russian and Connaught induced the highest inhibition of cell proliferation and cytokine production, triggering values up to threefold higher than the other bacillus Calmette-Guérin strains. In contrast, Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the least efficacious. For RT4 all bacillus Calmette-Guérin strains inhibited cell proliferation to a similar extent and induced low levels of only interleukin-8 except the Danish and Glaxo strains, which were less efficacious. CONCLUSIONS: Russian and Connaught, which are evolutionarily early and late substrains, respectively, are the most efficacious bacillus Calmette-Guérin strains for inhibiting cell proliferation and inducing cytokine production. Glaxo is the least efficacious strain.
PURPOSE: Evolutionarily early and late bacillus Calmette-Guérin substrains are genetically distinct, showing different antigenic determinants. While it was suggested that this may influence the immunostimulatory effects of bacillus Calmette-Guérin as a vaccine in the context of tuberculosis, to our knowledge the impact of these genetic differences on the antitumor activity of bacillus Calmette-Guérin remains unknown. We compared the direct antitumor capacity and the ability to trigger cytokine production of 8 evolutionarily early and late BCG substrains in urothelial bladder cancer cell lines. MATERIALS AND METHODS: The T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of 3 evolutionarily early bacillus Calmette-Guérin substrains (Japan, Moreau and Russian) and 5 evolutionarily late strains (Connaught, Danish, Glaxo, Phipps and Tice). The inhibition of cell proliferation at different time points and the production of interleukin-6 and 8 in cell culture supernatants were measured. RESULTS: For T24 and J82 cells Russian and Connaught induced the highest inhibition of cell proliferation and cytokine production, triggering values up to threefold higher than the other bacillus Calmette-Guérin strains. In contrast, Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the least efficacious. For RT4 all bacillus Calmette-Guérin strains inhibited cell proliferation to a similar extent and induced low levels of only interleukin-8 except the Danish and Glaxo strains, which were less efficacious. CONCLUSIONS: Russian and Connaught, which are evolutionarily early and late substrains, respectively, are the most efficacious bacillus Calmette-Guérin strains for inhibiting cell proliferation and inducing cytokine production. Glaxo is the least efficacious strain.
Authors: J Alfred Witjes; Guido Dalbagni; Robert J Karnes; Shahrokh Shariat; Steven Joniau; Joan Palou; Vincenzo Serretta; Stéphane Larré; Savino di Stasi; Renzo Colombo; Marek Babjuk; Per-Uno Malmström; Nuria Malats; Jacques Irani; Jack Baniel; Tommaso Cai; Eugene Cha; Peter Ardelt; John Varkarakis; Riccardo Bartoletti; Martin Spahn; Francesca Pisano; Paolo Gontero; Richard Sylvester Journal: Urol Oncol Date: 2016-09-14 Impact factor: 3.498