Killed but Metabolically Active Mycobacterium bovis BCG retains the antitumor ability of live BCG
Secanella-Fandos S, Noguera-Ortega E, Olivares F, Luquin M, Julián E. J Urol. 2013 Dec 10. pii: S0022-5347(13)06077-1. doi: 10.1016/j.juro.2013.12.002. [Epub ahead of print]

Abstract

PURPOSE: Mycobacterium bovis BCG is the most effective treatment in high-risk noninvasive bladder cancer. Although BCG immunotherapy clearly reduces recurrence and progression rates, side effects are common, and cases of BCG infection have been described. For this reason, it is necessary to find safer alternatives to live BCG. In this study, we aimed to explore the possibility of using killed but metabolically active (KBMA)-BCG.

MATERIAL AND METHODS: T24, J82, and RT4 bladder tumor cell lines were cultured with live and treated (by irradiation or heat) BCG Connaught. The inhibition of cell proliferation and the production of cytokines in cell culture supernatants were measured. Furthermore, peripheral mononuclear blood cells (PBMCs) were also infected, and the production of different cytokines in the cell culture supernatants was analyzed. Both mycobacteria-activated PBMC and cell culture supernatants were then cultured with T24 cells to analyze whether they exhibited cytotoxic activity.

RESULTS: Gamma-irradiated BCG exhibited activity more similar to that of live BCG, in both inhibiting tumor growth and inducing the production of cytokines, than the rest of the BCG treatments. We demonstrated that irradiated BCG exhibits metabolic activity (and thus is considered KBMA-BCG) and that this is the treatment that most accurately preserves the mycobacteria structure. Furthermore, KBMA-BCG is able to induce the production of cytokines by infected PBMC, and both mycobacteria-activated PBMC and cell supernatants showed cytotoxic activity against tumor cells, retaining the antitumor capacity of live BCG.