ENHANCED ANTITUMOR EFFECT OF BACILLUS-CALMETTE-GUERIN IN COMBINATION WITH FIBRINOGEN ON URINARY-BLADDER TUMOR

Although intravesical instillation of Bacillus Calmette-Guerin (BCG) i s an established and effective therapy for superficial urinary bladder tumor (UBT), the current major problems are BCG-resistant UBT and rec urrence after BCG therapy. The injection of BCG and fibrinogen could b e expected to induce the formation of a fibrin mesh, which would trap BCG and prolong its antitumor action. The present study has been desig ned to investigate whether fibrinogen has the ability to augment antit umor activity of BCG against UBT. A single injection of BCG/fibrinogen solution into the subcutaneous tissue of C3H/He mice was performed. H istopathological examination revealed prolonged accumulation of BCG an d marked infiltration of inflammatory cells at the injected site, as c ompared with the injection of BCG or fibrinogen alone. When BCG was us ed in combination with gelatin sponge, prolonged BCG accumulation was also observed, but not many inflammatory cells were induced, as compar ed with injection of BCG/fibrinogen combination. When BCG/fibrinogen s olution was injected into MBT-2 murine UBT transplanted into C3H/He mi ce, the formation of fibrin fibers, which trap BCG, was induced, and m any inflammatory cells around the tumor were seen. A pronounced inhibi tory effect on tumor growth and prolonged survival of tumor-bearing mi ce were achieved, as compared with the injection of BCG alone. Dead BC G/fibrinogen solution had a modest inhibitory effect on the tumor grow th. This study suggests that combination treatment with BCG and exogen ous fibrinogen may prolong accumulation of BCG by trapping BCG in fibr in meshwork, and may induce marked infiltration of inflammatory cells into tumor stroma, causing marked regression of the tumor. The possibl e clinical implications of the combined use of BCG and fibrinogen are discussed.