Bacillus calmette-guerin Tokyo172 substrain for superficial bladder cancer: characterization and antitumor effect

We investigated the preparation of bacillus Calmette-Guerin (BCG) Tokyo172 substrain (Japan BCG Laboratory, Ltd., Tokyo, Japan) on the characteristics of bacilli and antitumor activity in a mouse model in comparison with a preparation of the Connaught substrain (Aventis Pasteur, Ltd., Toronto, Ontario, Canada).

Lyophilized BCG preparations of Tokyo172 and Connaught for superficial bladder cancer were tested. The number of bacilli and cfu per dose, dispersion, size and attachment to murine bladder tumor cells were determined after reconstitution. Antitumor activity was assessed by intradermal injection of tumor cells with various doses of either BCG preparation into the flanks of syngeneic mice, followed by the observation of tumor suppression and survival in mice.

Each dose of Tokyo172 had about half the bacilli in a dose of Connaught but the cfu content was about 13-fold higher for Tokyo172 than for Connaught. After reconstitution Tokyo172 bacilli were better dispersed with fewer aggregates than Connaught bacilli. Tokyo172 bacilli were about half as long as Connaught bacilli and Tokyo172 bacilli showed better attachment to tumor cells in vitro. In mice Tokyo172 achieved similar tumor suppression at a lower dose than Connaught.

High viability, good dispersion and efficient binding to tumor cells by BCG bacilli in the Tokyo172 preparation seem to be the main reasons for the lower clinical dose of this preparation compared with the Connaught preparation (18 vs 81 mg dry weight).