PURPOSE: Evolutionarily early and late BCG substrains are genetically distinct, displaying different antigenic determinants.
While it has been suggested that this fact may influence the immunostimulatory effects of BCG as a vaccine in the context of tuberculosis, the impact of these genetic differences on the antitumor activity of BCG remains unknown. Here, the direct antitumor capacity and the ability to trigger cytokine production of eight evolutionarily early and late BCG substrains on urothelial bladder cancer cell lines were compared.
MATERIAL AND METHODS: The T24, J82 and RT4 bladder tumor cell lines were cultured with different doses of three evolutionarily early BCG substrains (Japan, Moreau and Russian) and five evolutionarily late strains (Connaught, Danish, Glaxo, Phipps, and Tice). Both inhibition of cell proliferation at different time points and the production of interleukin (IL)-6 and IL-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 three-fold higher than the other BCG strains. In contrast, Glaxo and Phipps (for T24 cells) and Glaxo and Tice (for J82 cells) were the least efficacious. For RT4, all BCG strains inhibited cell proliferation to a similar extent and induced low levels of only IL-8 except for Danish and Glaxo strains, which were less efficacious.
CONCLUSIONS: Russian and Connaught, evolutionarily early and late substrains, respectively, are the most efficacious BCGs for both inhibition of cell proliferation and induction of cytokine production. Glaxo was the least efficacious strain.
Written by:
Secanella-Fandos S, Luquin M, Julián E. Are you the author?
Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Reference: J Urol. 2012 Sep 13. pii: S0022-5347(12)04880-X.
doi: 10.1016/j.juro.2012.09.049
PubMed Abstract
PMID: 22982433
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