Connaught and Russian Strains Showed the Highest Direct Antitumor Effects of Different Bacillus Calmette-Guerin Substrains

Purpose: Evolutionarily early and late bacillus Calmette-Guerin substrains are genetically distinct, showing different antigenic determinants. While it was suggested that this may influence the immunostimulatory effects of bacillus Calmette-Guerin as a vaccine in the context of tuberculosis, to our knowledge the impact of these genetic differences on the antitumor activity of bacillus Calmette-Guerin 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-Guerin 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-Guerin 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-Guerin 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-Guerin strains for inhibiting cell proliferation and inducing cytokine production. Glaxo is the least efficacious strain.