BACKGROUND: Antitumor effects of Bacillus Calmette-Guérin (BCG) against superficial urinary bladder cancer is known to be strong when BCG is directly infused into the bladder cavity. For expression of that effect, attachment of BCG to tumor cells is reported to be essential as the first step. Our study was conducted to elucidate the significance of attachment of BCG to tumor cells in inducing the antitumor effect. METHODS: BCG, Tokyo 172 strain, in the form of live bacilli, lyophilized bacilli, or autoclaved bacilli was co-cultured with MBT-2, mouse-origin transitional cell cancer cells. Various preparations of BCG were mixed with MBT-2 cells and transplanted to male C3H/He mice to see tumor growth-inhibiting effect. RESULTS: Both live and lyophilized BCG attached strongly to MBT-2 cells. The maximal attachment to the cells with live BCG occurred 24 hours earlier than with lyophilized BCG. When BCG was autoclaved, it lost the ability to attach to the cells. Lyophilized or autoclaved BCG exerted a marked tumor growth-inhibiting effects. This effect was equal to the Tokyo 172 strain and the Armand Frappier Canada strain. Histologically, a high degree of infiltration by macrophages was seen. CONCLUSIONS: The results indicated that coexistence of BCG, even as killed by autoclaving, with tumor cells activates local immunity. Accordingly, the significance of the attachment of BCG to tumor cells in intravesical infusion therapy is surmised to lie in the fact that it results in retention of the BCG at the reaction site. This may provide a clue on how to approach future development of safer and more stable BCG-derived antitumor drugs.
BACKGROUND: Antitumor effects of Bacillus Calmette-Guérin (BCG) against superficial urinary bladder cancer is known to be strong when BCG is directly infused into the bladder cavity. For expression of that effect, attachment of BCG to tumor cells is reported to be essential as the first step. Our study was conducted to elucidate the significance of attachment of BCG to tumor cells in inducing the antitumor effect. METHODS:BCG, Tokyo 172 strain, in the form of live bacilli, lyophilized bacilli, or autoclaved bacilli was co-cultured with MBT-2, mouse-origin transitional cell cancer cells. Various preparations of BCG were mixed with MBT-2 cells and transplanted to male C3H/He mice to see tumor growth-inhibiting effect. RESULTS: Both live and lyophilized BCG attached strongly to MBT-2 cells. The maximal attachment to the cells with live BCG occurred 24 hours earlier than with lyophilized BCG. When BCG was autoclaved, it lost the ability to attach to the cells. Lyophilized or autoclaved BCG exerted a marked tumor growth-inhibiting effects. This effect was equal to the Tokyo 172 strain and the Armand Frappier Canada strain. Histologically, a high degree of infiltration by macrophages was seen. CONCLUSIONS: The results indicated that coexistence of BCG, even as killed by autoclaving, with tumor cells activates local immunity. Accordingly, the significance of the attachment of BCG to tumor cells in intravesical infusion therapy is surmised to lie in the fact that it results in retention of the BCG at the reaction site. This may provide a clue on how to approach future development of safer and more stable BCG-derived antitumor drugs.
Authors: Gloria Esteso; Nacho Aguiló; Esther Julián; Omodele Ashiru; Mei M Ho; Carlos Martín; Mar Valés-Gómez Journal: Front Immunol Date: 2021-02-23 Impact factor: 7.561
Authors: Nina M G P de Queiroz; Fabio V Marinho; Ana Carolina V S C de Araujo; Julia S Fahel; Sergio C Oliveira Journal: Sci Rep Date: 2021-08-02 Impact factor: 4.379