MYCOBACTERIUM CELL-WALL - AN ALTERNATIVE TO INTRAVESICAL BACILLUS-CALMETTE-GUERIN (BCG) THERAPY IN ORTHOTOPIC MURINE BLADDER-CANCER

Purpose: The antitumor effect of intravesical mycobacterium cell wall (MCW) therapy on orthotopic and heterotopic bladder tumors in the mous e was assessed with magnetic resonance imaging (MRI). Materials and Me thods: The live bacillus Calmette Guerin (BCG) organism was replaced w ith a cell wall extract derived from the outer capsule of Mycobacteriu m phlei. This alternative form of intravesical therapy was used with t he aim of reducing the toxicity associated with the live mycobacterium organism without compromising efficacy. Response to multiple doses of intravesical MCW and BCG was assessed in mice with established MBT-2 tumors after transurethral tumor implantation. Results: Serial MRI of BCG-treated mice revealed significant tumor regression. The MR images correlated well with the corresponding histology of the whole mount bl adder sections. Treatment with MCW also resulted in significant inhibi tion of tumor growth compared with control untreated animals (p <0.05) although the antitumor effect was less pronounced than that of live B CG. Treatment was well tolerated in the MCW group with no apparent ill effects. Flow cytometric (FCM) analysis of bladder washings with phen otype-specific monoclonal antibodies revealed predominantly a CD3+ T c ell infiltrate in the control and BCG-treated as well as the MCW-treat ed mice. The CD4+ (helper/inducer) subset of T cells predominated over the CD8+ (suppressor/cytotoxic) subset in both the BCG- and MCW-treat ed animals, and the CD4+/CD8+ ratio in both of the treated groups diff ered significantly from that of the control untreated groups. Conclusi on: Intravesical MCW appears to invoke a similar inflammatory response in the mouse bladder mucosa as the live BCG organism and retains an a ntitumor action. It deserves further evaluation as a potential antitum or agent against bladder cancer. A Phase II clinical trial is now unde rway.